Selective perfusion of ischemic myocardium during coronary venous retroinjection: a study of the causative role of venoarterial and venoventricular pressure gradients

Coronary venous retroinjection is often associated with preferential distribution of flow to ischemic myocardium. The purpose of this study was to define the mechanism of such retrodistribution of flow. In 24 anesthetized open chest dogs, Monastral blue dye (10 ml) was injected by way of a balloon catheter in the distal great cardiac vein as a marker for retrograde flow distribution. The injection rate (0.6 to 2.4 ml/s) was adjusted such that systolic pressure in the anterior interventricular vein ranged between 60 and 85 mm Hg. In 11 dogs with no ischemia and normal myocardial perfusion pressure (96 +/- 8 mm Hg), no myocardial staining occurred despite retrograde filling of epicardial veins. One minute after occlusion of the left anterior descending coronary artery, dye injections caused selective staining of the cyanotic area in 15 of 18 episodes, sparing the normal myocardium within the zone of retroperfused veins. In five dogs, with the arterial pressure less than 55 mm Hg, retroinjection resulted in homogeneous staining of all the myocardium drained by the retroperfused veins. Selective staining of the ischemic myocardium caused by retroinjection was associated with the following pressure gradients: during systole from the anterior interventricular vein to the occluded coronary artery, 31 to 58 mm Hg, and during diastole from the retroperfused veins to the left ventricular chamber, 9 to 28 mm Hg. There was no diastolic venoarterial gradient in the ischemic myocardium. In normal myocardium, retroinjection did not reverse the arteriovenous pressure gradient. In conclusion, retrograde flow is primarily directed to myocardium with low anterograde perfusion pressure. Selective retrograde penetration of acutely ischemic myocardium can thus be achieved by a mechanism consistent with the development of venoarterial and venoventricular pressure gradients.     

Reduction of infarct size induced by pressure-controlled intermittent coronary sinus occlusion

The effect of pressure-controlled intermittent coronary sinus (CS) occlusion on myocardial infarction (MI) size was evaluated. A device for this purpose was developed that consisted of a balloon catheter and pump system that produced controlled, intermittent occlusion of the CS and used CS pressure as a feedback to determine the duration of occlusion. It was hypothesized that proper selection of occlusion and nonocclusion times would both facilitate improved retrograde flow to ischemic areas and allow for more complete venous washout of metabolites. In 13 treated dogs and 12 control dogs before treatment, myocardium at risk of MI was estimated by injection of technetium-labeled microspheres. Intermittent CS occlusion was then begun, 15 minutes after coronary artery occlusion, and continued until termination of the experiment 6 hours later. Postmortem determination of infarct size was performed using the triphenyltetrazolium chloride staining technique. Intermittent CS occlusion begun 15 minutes after coronary artery occlusion and continued for 6 hours resulted in a 45% average reduction in MI size (p <0.001). During CS occlusion, the sinus systolic mean pressure increased from 10 to 44 mm Hg, while the distal coronary artery mean pressure increased by an average of 36% (from 22 to 30 mm Hg, p <0.05). These results suggest intermittent occlusion may be an effective treatment for evolving MI. This therapy, used alone or combined with other therapies (e.g., administration of pharmacologic agents), appears to have great clinical potential.     

The efficacy of intermittent coronary sinus occlusion in the absence of coronary artery collaterals

The purpose of this study was to evaluate the efficacy of time-controlled intermittent coronary sinus occlusion (ICSO) in preserving regional and global mechanical function during acute ischemia in an animal preparation without significant arterial collateral vessels. Seventeen (eight control, nine ICSO) swine heart preparations undergoing extracorporeal coronary perfusion in situ were subjected to ligation of the left anterior descending coronary artery (LAD) distal to the first major diagonal branch. Data were obtained before and immediately after coronary artery ligation in both animal groups. ICSO, 15 sec of occlusion alternating with 5 sec of release, was then begun in the treatment group. Additional data were obtained in both control and treatment groups at 15 min intervals for 1 hr starting immediately after coronary artery ligation. Global left ventricular function was assessed by shifts in left ventricular end-diastolic pressure and left ventricular dP/dt with left ventricular systolic pressure maintained at about 100 mm Hg. Regional mechanical function was evaluated with transmurally placed ultrasonic crystals. Pressure was also measured directly in the coronary sinus and LAD distal to the ligature. Regional myocardial blood flow was measured in the ischemic bed using 9 micron diameter radiolabeled microspheres injected before, immediately after, and 60 min after coronary artery ligation in both treated and control animals. LAD mean pressure measured distal to the ligation (less than 16 mm Hg) and ischemic bed myocardial blood flow (less than 0.01 ml/g/min) confirmed the absence of significant arterial-arterial collaterals in this preparation. Mean coronary sinus pressure increased significantly (p less than .001) in treated animals during ICSO (e.g., 11.2 +/- 1.6 to 66.2 +/- 10.0 mm Hg at 15 min after coronary ligation). Mean LAD pressure distal to the coronary ligature also increased during ICSO (14.2 +/- 1.2 to 26.8 +/- 1.6 mm Hg), with a similar but delayed rate of pressure rise. No significant differences in left ventricular end-diastolic pressure or left ventricular dP/dt were noted between control or treated animals after coronary ligation. Ischemic bed systolic wall thickening, present before coronary ligation, was not present after occlusion and was not improved during intermittent coronary sinus occlusion in the treatment group. We conclude that in an animal preparation without significant collateral circulation, intermittent coronary sinus occlusion is incapable of restoring regional or global left ventricular mechanical function during conditions of acute ischemia.     

Effects of pressure-controlled intermittent coronary sinus occlusion on regional ischemic myocardial function

Pressure-controlled intermittent coronary sinus occlusion has been reported to reduce infarct size in dogs with coronary artery occlusion, possibly because of increased ischemic zone perfusion and washout of toxic metabolites. The influence of this intervention on regional myocardial function was investigated in open and closed chest dogs. In six open chest dogs with severe stenosis of the left anterior descending coronary artery and subsequent total occlusion, a 10 minute application of intermittent coronary sinus occlusion increased ischemic myocardial segment shortening from 5.5 +/- 1.2 to 8.2 +/- 2.6% (NS) and from -0.1 +/- 2.1 to 2.3 +/- 1.2% (NS), respectively. In eight closed chest anesthetized dogs, intermittent coronary sinus occlusion was applied for 2.5 hours between 30 minutes and 3 hours of intravascular balloon occlusion of the proximal left anterior descending coronary artery. Standardized two-dimensional echocardiographic measurements of left ventricular function were performed to derive systolic sectional and segmental fractional area changes in five short-axis cross sections of the left ventricle. Fractional area change in all the severely ischemic segments (less than 5% systolic wall thickening) was -4.0 +/- 4.7% at 30 minutes after occlusion, and increased with subsequent 60 and 150 minutes of treatment to 13.1 +/- 3.3 and 7.0 +/- 3.3%, respectively (p less than 0.05). At the most extensively involved low papillary muscle level of the ventricle, regional ischemic fractional area change was increased by intermittent coronary sinus occlusion between 30 and 180 minutes of coronary occlusion from -0.4 +/- 0.1 to 14.4 +/- 4% (p less than 0.05), whereas a further deterioration was noted in untreated dogs with coronary occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adverse effects of circumflex coronary artery occlusion on blood flow to remote myocardium supplied by a stenosed left anterior descending coronary artery in anesthetized open-chest dogs

Left anterior descending coronary artery occlusion in open-chest dogs causes a decrease in endocardial blood flow to the remote posterior bed supplied by a stenosed left circumflex coronary artery. To determine if "remote" myocardial ischemia also occurred in the anterior bed after circumflex occlusion, myocardial blood flow (radiolabeled microspheres) and hemodynamics were measured before and after circumflex occlusion in the presence of a stenosed left anterior descending artery (gradient: 28 +/- 2 mm Hg) in 10 open-chest dogs. Aortic pressure fell from 108 +/- 3 to 100 +/- 3 mm Hg (p = 0.02) and mean distal left anterior descending coronary artery pressure fell from 81 +/- 4 to 69 +/- 5 mm Hg (p = 0.02) after circumflex occlusion. Transmural flow to normal myocardium supplied by unstenosed and unoccluded coronary arteries increased from 0.69 +/- 0.04 to 0.84 +/- 0.04 ml/min/gm (p less than 0.0001) after circumflex occlusion. Although epicardial flow to the remote anterior bed supplied by the stenosed left anterior descending coronary artery increased after left circumflex occlusion (0.61 +/- 0.03 to 0.73 +/- 0.04 ml/min/gm, p = 0.004), remote anterior bed endocardial flow did not increase, and the remote bed endocardial:epicardial blood flow ratio decreased from 0.98 +/- 0.06 to 0.78 +/- 0.10 (p less than 0.05). Therefore, in this model, remote anterior bed ischemia, relative to the normal myocardial flow response, developed when the left circumflex coronary artery was occluded in the presence of the stenosed left anterior descending coronary artery.     

Paradoxical increase of ventricular fibrillation threshold in response to coronary sinus obstruction

We determined the ventricular fibrillation threshold (VFT) changes in response to graded coronary sinus (CS) obstruction in 13 chloralose-anesthetized dogs with fixed heart rate (150 min-1, mean systemic arterial pressure (80 mm Hg), and cardiac index (100 ml/min.kg-1 body weight). VFT in milliamperes (VFTmA) increased linearily with CS pressure (CSP) increases up to 41.2 +/- 1.4 mm Hg (VFTmA = 6.5 + 0.14 CSP mm Hg, p less than 0.01). Total coronary venous effluent (CBF) did not change significantly, suggesting compensatory coronary vasodilation. Myocardial O2 consumption also remained unchanged. At higher CSP, both CBF and VFT declined precipitously (VFTmA = 20.9 - 0.27 CSP mm Hg, p less than 0.02). With simultaneous increases of systemic arterial along with CSP, VFT increased again along with the CSP-induced reduction of gradient until it reached 42.8 +/- 3.2 mm Hg. We conclude that with coronary venous obstruction, despite coronary perfusion gradient reduction to about 40 mm Hg, CBF remains constant. This constant flow vasodilation is associated with substantial (82%) VFT increase. The mechanism may involve enhanced homogeneity of CBF distribution and increased extracellular fluid.     

Effect of intracoronary nitroglycerin administration on phasic pattern and transmural distribution of flow during coronary artery stenosis.

BACKGROUND. Nitroglycerin is effective in relieving myocardial ischemia; however, intracoronary nitroglycerin often fails to relieve angina and has been reported to have deleterious effects on subendocardial blood flow. To understand the mechanisms involved, we evaluated the direct effect of nitroglycerin on coronary circulation of the ischemic hearts. METHODS AND RESULTS. We measured the phasic pattern of intramyocardial coronary arterial flow with an 80-channel, 20-MHz pulsed Doppler ultrasound flowmeter under moderate to severe coronary artery stenosis (distal perfusion pressure approximately 45 mm Hg group 1, n = 6) and transmyocardial blood flow distribution using radioactive microspheres while maintaining coronary pressure at a low constant level (40 mm Hg, group 2, n = 6). In anesthetized open-chest dogs, the left main coronary artery was perfused directly from the right carotid or femoral artery. In this bypass circuit, pressure was controlled with an occluder or a reservoir was connected to the circuit. In group 1, the systolic and diastolic pressures distal to the stenosis decreased significantly after intracoronary administration of nitroglycerin at maximal coronary flow from 66.5 +/- 18.5 to 56.5 +/- 13.8 mm Hg (p less than 0.01) and from 36.6 +/- 14.4 to 27.5 +/- 8.9 mm Hg (p less than 0.01), respectively. The phasic pattern of the septal artery flow was predominantly diastolic and was characterized by systolic reverse flow even in the absence of stenosis. Coronary stenosis increased systolic reverse flow. Nitroglycerin increased diastolic forward flow (p less than 0.05) but augmented systolic reverse flow markedly (p less than 0.001). In group 2, nitroglycerin increased subepicardial flow (p less than 0.05) but failed to increase subendocardial flow. With the administration of nitroglycerin, the subendocardial-to-subepicardial flow ratio decreased significantly from 0.73 +/- 0.19 to 0.32 +/- 0.14 (p less than 0.01). CONCLUSIONS. The increased systolic reverse flow after intracoronary administration of nitroglycerin may be closely related to failure of subendocardial blood flow to increase with increase subepicardial flow.     

Retrograde lysis of coronary artery thrombus by coronary venous streptokinase administration

This study examined whether an occlusive thrombus within a coronary artery can be lysed by streptokinase retroperfusion into the associated regional coronary vein. Experimental coronary artery thrombosis was induced in 15 closed chest dogs by placing a small copper coil at a proximal site of the left anterior descending coronary artery. Total thrombotic obstruction of this artery was verified within 10 to 60 minutes (38.0 +/- 15.8, mean +/- standard deviation) and streptokinase was administered within 94.0 +/- 17.4 minutes from coil insertion at an average rate of 42 IU/kg per minute by one of three modes: 1) intermittent 10 minute direct coronary venous retroinfusion (five dogs); 2) continuous infusion into the pumping circuit of synchronized phased retroperfusion of the great cardiac vein with arterial blood (five dogs); and 3) for comparison, streptokinase administered intravenously (five dogs). The intracoronary thrombus was fully lysed and anterograde reperfusion established within 51.0 +/- 18.7 minutes by intermittent streptokinase retroinfusion, and in 50.0 +/- 6.1 minutes by streptokinase supplemented synchronized retroperfusion (50.5 +/- 13.2 minutes for pooled retrograde coronary venous delivery). Lysis was also induced by systemic streptokinase, but the time to lysis was significantly longer and more variable (131.6 +/- 60.6 minutes) than with retrograde administration (p less than 0.01). The retroperfusion modality appears the preferable technique because it provides early thrombolysis and, at the same time, improves cardiac function and maintains myocardial viability of the jeopardized ischemic zone pending achievement of full reflow. Thus, streptokinase retroperfusion, if promptly instituted, may be a useful complemental nonsurgical treatment of evolving acute myocardial infarction after thrombotic coronary artery occlusion.     

Effects of pulsed external augmentation of diastolic pressure on coronary and systemic hemodynamics in patients with coronary artery disease

The purpose of this study was to define the effects of pulsed external diastolic pressure augmentation on coronary and systemic hemodynamics in 14 men with coronary artery disease and normal left ventricular function. Coronary sinus and great vein blood flow (thermodilution) and systemic hemodynamics were measured before, during, and after timed lower extremity compression, augmenting peak diastolic pressure to within 5 mm Hg of systolic pressure. Systolic and diastolic pressure-time indices were calculated from the high-fidelity micromanometer left ventricular-aortic recordings. External counterpulsation increased mean arterial pressure (108 +/- 11 [1 SD] to 114 +/- 12 mm Hg, p less than 0.01) and the diastolic pressure-time index (440 +/- 51 to 498 +/- 82 units, p less than 0.01), with no change in the systolic pressure-time index, absolute coronary sinus, or great cardiac vein blood flow. External diastolic pressure augmentation did not affect heart rate, right heart hemodynamics, cardiac output, or calculated myocardial oxygen consumption. An unanticipated finding was a greater than or equal to 10% reduction in peak systolic pressure during external diastolic pressure augmentation in 8 of 14 patients. Despite minimal changes in absolute myocardial blood flow and oxygen consumption, the increase in the diastolic pressure-time/systolic pressure-time index ratio suggests that subendocardial perfusion may be favorably influenced by diastolic pressure augmentation and may explain the previously reported clinical benefits of external counterpulsation in some patients with ischemic heart disease.     

Myocardial function and transmural blood flow during coronary venous retroperfusion in pigs.

BACKGROUND. The degree of recovery of regional myocardial contraction during coronary venous retroperfusion has not been well established, particularly in the absence of coronary collateral channels. Therefore, the maximal functional benefit attainable with coronary venous retroperfusion was assessed in pigs by means of using selective pump retroperfusion of the left anterior descending vein, with venting of the left anterior descending artery to zero pressure. METHODS AND RESULTS. In eight anesthetized open-chest pigs during selective left anterior descending venous retroperfusion over a range of retroperfusion flows, regional myocardial function (percent systolic wall thickening by sonomicrometry) increased progressively to an average of 62% of control values at a retroperfusion flow rate 200% of control arterial flow. Progressive thickening of the end-diastolic dimension of the anterior wall was observed with increasing retroperfusion flow (from 8.7 +/- 0.9 to 10.7 +/- 2.3 mm, p less than 0.001). Perfusion pressures within the left anterior descending vein increased linearly with increased retroperfusion flow rates (up to 132 +/- 57 mm Hg with retroperfusion flow 200% of control). A gradual increase of retrograde left anterior descending arterial outflow was observed with increasing retroperfusion flows; however, the absolute amount (maximum, 8.3 +/- 4.1 ml/min) was much too low to explain the extent of functional recovery. Transmural myocardial capillary blood flows in the anterior wall with retroperfusion flows of 100% and 200% of control arterial flow were 0.22 and 0.42 ml/min/g with corresponding subendocardial blood flows of 0.14 and 0.29 ml/min/g; ratios of endocardium to epicardium were 0.51 and 0.61, respectively. Thus, capillary blood flows during selective retroperfusion were relatively low despite considerable restoration of regional systolic wall thickening, and a significant difference was noted in the slopes of the relations between regional systolic wall thickening and myocardial blood flow during retroperfusion and anterograde arterial perfusion (p less than 0.05). With retrograde injection of silicone elastomer at different retroperfusion pressures (50, 75, and 100 mm Hg) in three pigs, capillaries were well visualized, and profuse intramyocardial venous anastomotic connections were seen at the highest retroperfusion pressure (100 mm Hg), whereas there was filling of small venules but little capillary filling at the lowest retroperfusion pressure (50 mm Hg). CONCLUSIONS. Considerable recovery of regional myocardial function with low regional capillary blood flows were observed during acute venous retroperfusion with high retroperfusion flows with arterial blood. These findings together with low levels of retrograde arterial outflow and visualization of retrograde capillary filling with a rich venous network provide evidence for possible oxygen delivery via the intramyocardial venous plexus.     

Low zero-flow pressure and minimal capacitance effect on diastolic coronary arterial pressure-flow relationships during maximum vasodilation in swine

During maximum dilation with adenosine in dogs, the diastolic coronary pressure at which flow ceases (Pzf) has been observed to be up to 27 mm Hg above coronary sinus and right atrial pressures. We studied swine to measure the Pzf and to determine the effects of interventions that change collateral flow and coronary capacitance. In 44 swine, the left anterior descending coronary artery (LAD) was instrumented with two catheters, a hydraulic occluder, and a flowmeter. Late diastolic and mean pressure-flow relationships were constructed at a series of pressures produced by partial LAD occlusions during maximum vasodilation. The late diastolic Pzf was 7.0 +/- 2.2 mm Hg (mean +/- SD), less than 4 mm Hg above right atrial pressure; the mean Pzf was 12.1 +/- 3.1 mm Hg, less than 9 mm Hg above right atrial pressure. The Pzf in the LAD did not change significantly (1) during transient simultaneous occlusion of the right coronary artery (RCA) in seven swine (late diastolic Pzf with the RCA open was 6.6 +/- 1.5 mm Hg and with the RCA closed it was 6.0 +/- 1.5 mm Hg), (2) during increased left ventricular systolic pressure (LVSP) in seven swine (late diastolic Pzf with LVSP of 123 mm Hg was 5.5 +/- 2.2 mm Hg and with LVSP of 184 mm Hg it was 7.3 +/- 2.8 mm Hg), or (3) during increased heart rate in eight swine (late diastolic Pzf at heart rate of 107 per minute was 10.8 +/- 2.9 mm Hg and at 180 per minute it was 12.7 +/- 2.1 mm Hg). Similar results were obtained from analysis of the mean pressure and flow data. The Pzf in the LAD of swine is very close to right atrial pressure, and it did not change significantly during interventions that would modify collateral flow (reduced by RCA occlusion and enhanced by increased LVSP) and coronary capacitance (increased LVSP and increased heart rate). This low Pzf is beneficial in maintaining flow at lower coronary arterial perfusion pressures.     

Collateral conductance changes during a brief coronary occlusion in awake dogs

Function of the coronary collateral circulation during the course of a single abrupt coronary occlusion was evaluated in awake dogs instrumented over the long term. Studies were performed approximately 2 weeks after collateral development had been stimulated in the dogs by partial stenosis of the proximal left circumflex coronary artery. The pressure drop from the central aorta to the distal circumflex coronary artery was measured continuously. Under control conditions and at 30 sec and 4 min of a single abrupt complete circumflex occlusion, myocardial blood flow was determined by a radioactive microsphere technique. Coronary collateral conductance was calculated as mean collateral blood flow divided by the mean drop in pressure. The following was noted in dogs that developed collateral vessels: during the coronary occlusion, mean distal circumflex coronary pressure increased from 42 +/- 9 to 49 +/- 10 mm Hg (p less than or equal to .01); mean collateral flow increased from 0.78 +/- 0.30 to 0.84 +/- 0.33 ml/min/g (p less than or equal to .05); the endocardial/epicardial flow ratio increased from 0.77 +/- 0.36 to 1.04 +/- 0.25 (p less than or equal to .01); and the coronary collateral conductance increased significantly from 0.017 +/- 0.017 to 0.021 +/- 0.021 (ml/min/g)/mm Hg (p less than or equal to .005). These data suggest that during a brief occlusion of a major coronary artery, immature coronary collateral channels do not reach maximal function immediately after the occlusion. Rather, coronary collateral conductance increases with time and may be associated with improved transmural perfusion of the myocardium.     

Effects of nitroglycerin-induced hypotension on myocardial blood flow in a two vessel occlusion-stenosis anesthetized canine model

The effects of acute occlusion of the left anterior descending coronary artery on regional blood flow (microspheres) to the remote bed supplied by either an unstenosed or a stenosed circumflex coronary artery were assessed during the infusion of intravenous nitroglycerin in 11 open chest barbiturate-anesthetized mongrel dogs. Left anterior descending coronary artery occlusion in the presence of an unstenosed left circumflex artery during nitroglycerin infusion caused systolic aortic and distal circumflex pressure to decrease significantly from 98 +/- 4 to 91 +/- 3 and from 99 +/- 4 to 92 +/- 3 mm Hg, respectively. Remote circumflex bed flow was unchanged. The infusion of intravenous nitroglycerin in the presence of a left circumflex stenosis (gradient 31 +/- 3 mm Hg) reduced systolic aortic and distal circumflex pressure to 98 +/- 2 (p = 0.001) and 71 +/- 4 mm Hg (p = 0.001), respectively, and lowered remote circumflex bed endocardial flow from 1.00 +/- 0.08 to 0.79 +/- 0.07 ml/min per g (p = 0.001). When the left anterior descending coronary artery was occluded under these conditions, systolic aortic and distal left circumflex pressure decreased to 89 +/- 3 (p = 0.005) and 62 +/- 4 mm Hg (p = 0.08), respectively. Remote circumflex artery bed endocardial and transmural flow were significantly reduced to 0.58 +/- 0.07 (p = 0.01) and 0.65 +/- 0.07 ml/min per g (p = 0.03), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of the calcium antagonist nisoldipine on coronary circulation and myocardial ischemia in temporary coronary occlusion

Sixteen patients undergoing PTCA of a significant lesion of the left anterior descending coronary artery received either 0.3 mg nisoldipine or placebo intravenously. Immediately before and during balloon inflation the following parameters were measured: aortic pressure, post-stenotic pressure, coronary occlusion pressure, diastolic pulmonary artery pressure, coronary sinus flow (thermodilution), and intracoronary ECG. After placebo there were no statistically significant changes. Nisoldipine led to a decrease in aortic pressure from 109 +/- 12 to 93 +/- 11 mm Hg (p less than 0.05) before, and from 103 +/- 14 to 92 +/- 8 mm Hg (NS) during balloon inflation. In contrast, coronary occlusion pressure remained unchanged. Heart rate increased from 80 +/- 13 to 96 +/- 16/min before (p less than 0.05), and from 87 +/- 18 to 97 +/- 17/min during balloon inflation (NS). Coronary sinus flow was increased from 95 +/- 16 to 116 +/- 13 ml/min before balloon inflation (p less than 0.01), and from 70 +/- 25 to 86 +/- 26 ml/min during balloon inflation (NS). ST-segment depression or elevation, severity of angina pectoris, and the diastolic pulmonary artery pressure remained unchanged. Thus, 0.3 mg nisoldipine led to a peripheral vasodilatation. While the aortic pressure decreased, coronary occlusion pressure remained unaffected. This could be explained by a marked dilatation of collateral vessels due to nisoldipine. However, myocardial ischemia remained unaffected as a result of the constant coronary occlusion pressure.     

The effectiveness of various modes of nonsynchronized retrovenous perfusion in salvage of ischemic myocardium in the pig.

The effectiveness of intermittent coronary sinus occlusion was compared to a new non-electrocardiogram-synchronized coronary sinus retroperfusion system in terms of ability to reduce myocardial infarct size. In 40 anesthetized, open-chest pigs the left anterior descending coronary artery was occluded for 4 h and then reperfused for 1 h. In the arterial group, the coronary sinus was intermittently occluded (5 s inflation, 5 s deflation) with retroperfusion of arterial blood at 60 mL/min during balloon inflation. In the venous group, the protocol was identical to the arterial group except that venous blood was retroperfused at the same flow rate during balloon inflation. In the intermittent coronary sinus occlusion group, the coronary sinus was similarly occluded, but there was no active retroperfusion. In the control group, no intervention was performed. In the three experimental groups, retroperfusion was maintained throughout the 4 h occlusion period. Infarct size, assessed by tetrazolium staining and expressed as a percentage of the in vivo area at risk, was greater in control animals (86.3 +/- 7.5%) compared to either arterial (44.1 +/- 12.9%; P less than 0.001) or venous groups (57.7 +/- 15.5%; P less than 0.001) but not compared to the intermittent coronary sinus occlusion group (78.0 +/- 10.2%; not significant). Active retroperfusion with arterial blood did not achieve significantly greater salvage compared to active retroperfusion with venous blood (not significant), although both produced significantly greater salvage than intermittent coronary sinus occlusion (P less than 0.03). Mean coronary sinus pressure was 56.1 +/- 25.4, 38.8 +/- 5.6 and 17.1 +/- 6.4 mmHg in the arterial, venous and intermittent coronary sinus occlusion groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Beneficial effects of atrioventricular synchrony in dogs with right coronary artery embolization, and complete heart block

Complete heart block complicating right ventricular infarction frequently is accompanied by shock. Hemodynamic responses to different pacing modes were studied in six anesthetized, closed chest dogs following right coronary artery embolization with mercury and heart block induced by repetitive trans-septal DC shock. Hemodynamics were recorded at control, following right coronary artery embolization, during atrioventricular sequential pacing (DVI) and ventricular pacing (VVI). With respect to the hemodynamics recorded during VVI and DVI pacing; (1) The mean arterial pressure increased by 29.4% during DVI pacing (92.1 +/- 31.3 mm Hg vs 73.4 +/- 28.9 mm Hg p less than 0.005). This increase was primarily due to an augmentation in systolic arterial pressure. (2) The left ventricular end diastolic pressure increased by 35.8% during DVI pacing (16.3 +/- 5.3 mm Hg vs 12.0 +/- 4.3 mm Hg p less than 0.01). (3) Cardiac output improved by 33.8% during DVI pacing (2.34 +/- 0.75 L/min vs 1.76 +/- 0.59 L/min, p less than 0.0005). This was a consistent improvement in cardiac output with a narrow range of 27.1% to 39.0%. (4) There were no significant changes in right atrial, pulmonary, pulmonary capillary wedge pressures or in systemic vascular resistance. In dogs with right coronary artery occlusion and complete heart block DVI pacing is clearly superior to VVI pacing. This is probably because the atrial contribution to ventricular filling, in this model, is critically important to maintain an adequate cardiac output.     

Effects of nitroglycerin and nifedipine on coronary and systemic hemodynamics during transient coronary artery occlusion

Nitroglycerin (NTG) and nifedipine (NIF) have the potential to augment coronary blood flow in addition to reducing peripheral determinants of myocardial oxygen demand as a synergistic protective mechanism during ischemia. To examine these effects, systemic and coronary hemodynamic responses were measured continuously before and during brief periods of myocardial ischemia induced by left anterior descending coronary balloon occlusion in 26 patients undergoing angioplasty (PTCA). Data were compared for two matched occlusion periods, one control and one "drug" occlusion. In 17 patients (NTG group), 200 micrograms of intracoronary NTG was given immediately before coronary occlusion. In nine patients (NIF group), 10 mg of sublingual NIF was given 15 minutes before the "drug" occlusion. NTG significantly but transiently reduced mean arterial pressure (91 +/- 11 to 82 +/- 15 mm Hg, p less than 0.05) and augmented basal coronary blood flow (95 +/- 38 to 127 +/- 54 ml/min, p less than 0.05) but did not alter great vein blood flow (59 +/- 29 vs 61 +/- 29 ml/min) or coronary occlusion pressure (25 +/- 7 to 24 +/- 7 mm Hg) during ischemia. NIF significantly reduced systolic, diastolic, and mean arterial pressure (119 +/- 21 to 95 +/- 8 mm Hg, p less than 0.001) and heart rate-pressure product from control. NIF maintained basal great vein blood flow (125 +/- 41 to 106 +/- 57 ml/min) during reduced myocardial oxygen demand, but did not affect great vein blood flow (73 +/- 29 to 79 +/- 37 ml/min) or coronary occlusion pressures during ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic and metabolic effects of sodium nitroprusside on the performance and metabolism of regional ischemic myocardium;.

To assess the effects of sodium nitroprusside (5-10 mug/min) on total and regional cardiac performance, energetics, and lactate metabolism during acute ischemia, studies were performed in 21 open-chest dogs. For studies of regional function and metabolism, length gauges were sutured to the epicardial surface and an epicardial vein adjacent to the artery to be occluded was cannulated. Following occlusion of the left anterior descending coronary artery, cardiac output, mean arterial pressure, epicardial vein blood flow, and systolic shortening of the ischemic segment decreased significantly, In the blood samples from the ischemic zone, but not in those from the coronary sinus, lactate extraction shifted to production. In seven control dogs these alterations persisted throughout the experiment. In 14 animals treated with nitroprusside, cardiac output increased while peripheral resistance and mean arterial pressure decreased. Systolic shortening in the ischemic segment increased from 1.10 +/- 0.24 (SEM) to 1.77 +/- 0.30 mm (P less than 0.005). In eight dogs, regional venous outflow increased from 1.9 +/- 0.1 to 3.0 +/- 0.4 ml/min despite a slight reduction in mean arterial pressure. Concomitantly, regional negative lactate balance was reduced from -61.0 +/- 20.0 to -23.2 +/- 5.7% (P less than 0.05). These results indicate that nitroprusside significantly improves both total cardiac performance and the mechanical performance of regional ischemic myocardium. Moreover, this improvement in mechanical function occurred concomitantly with apparent increase in regional perfusion and reduction in lactate production, suggesting that nitroprusside simultaneously alleviates ischemia.     

Coronary hemodynamics during percutaneous transluminal coronary angioplasty

The hemodynamic consequences of multiple transient occlusions (9.8 ± 3.7 seconds) of the left anterior descending coronary artery were assessed in 15 conscious patients during percutaneous transluminal coronary angioplasty. Thermodilution coronary venous blood flow, measured in the great cardiac vein, decreased from control values of 75.9 ± 24 ml/min to 50.9 ± 21.9 with coronary occlusion (probability [p] < 0.00001) and increased to 101.6 ± 34.3 after release of occlusion (p < 0.00001). Changes in coronary sinus blood flow, measured simultaneously, reflected the alterations in the great cardiac vein. Restoration of postocclusion blood flow to control values occurred in 18.2 ± 6.7 seconds, and is compatible with reactive hyperemia rather than sustained improvement in resting coronary blood flow. Flow repayment during reactive hyperemia exceeded flow debt incurred during coronary occlusion by 288.4 ± 106 percent (p < 0.05). The increase in reactive hyperemic flow after initial coronary occlusion (24.2 ± 15.7 ml/min) was less than that after final occlusion (42.2 ± 10.1, p < 0.05). This suggests an initial limitation of reactive hyperemia by persistent coronary stenosis. In all patients, reactive hyperemia accentuated the trans-stenotic coronary ostial to distal coronary arterial pressure gradient. Compared with a control value of 53.5 ± 7.7 percent, the great cardiac vein oxygen saturation transiently decreased to 49.3 ± 7.0 percent (p < 0.001) on release of the occlusion and then increased to 62.5 ± 5.2 percent (p < 0.001) during reactive hyperemia. A small reduction in aortic pressure from 96.4 ± 10.2 mm Hg to 89.9 ± 10.9 mm Hg(p < 0.00001) was observed during occlusion. A reduction in first derivative of left ventricular pressure (dP/dt) during coronary occlusion, in three patients in whom it was measured, suggests that the decrease in systemic pressure is due to transient ischemic myocardial dysfunction rather than to peripheral arteriolar vasodilation. These observations are relevant to the performance of coronary angioplasty, and to the understanding of the physiology of transient coronary occlusion in conscious patients.     

Effects of aminophylline in the conscious dog after coronary occlusion

The effects of aminophylline were examined in 19 conscious dogs subjected to coronary arterial occlusion. Measurements were made of left ventricular pressure and its first derivative (dP/dt), segment length and the velocity of segment length shortening in normal and severely ischemic zones. Regional blood flow was measured in these zones using the radioactive microsphere technique. Coronary occlusion increased heart rate, mean arterial pressure and left ventricular end-diastolic pressure but did not change left ventricular systolic pressure or dP/dt significantly. It also resulted in increased end-diastolic segment length and reduced segment length shortening (114 ± 6 percent, that is, paradoxical bulging) associated with marked reduction of blood flow to ischemic myocardium. Aminophylline, 1 mg/kg per min for 9 to 15 minutes administered after occlusion, increased heart rate 6 ± 2 beats/min, mean arterial pressure 5 ± 1 mm Hg, left ventricular systolic pressure 9 ± 2 mm Hg and left ventricular dP/dt 670 ± 50 mm Hg/s while reducing left ventricular end-diastolic pressure by 3.4 ± 0.3 mm Hg. In severely ischemic zones aminophylline increased transmural blood flow by 21 ± 8.0 percent (p < 0.02), reduced end-diastolic segment length by 0.23 ± 0.05 mm (p < 0.01) and reduced paradoxical bulging by 0.15 ± 0.06 mm (p < 0.02). Thus, in the presence of coronary arterial occlusion, aminophylline increased mean arterial pressure, left ventricular dP/dt and heart rate while reducing left ventricular end-diastolic pressure. In severely ischemic myocardium aminophylline appeared to exert a salutary effect and improved both regional perfusion and function.