Role of afterload in determining regional right ventricular performance during coronary underperfusion in dogs

The relationship between coronary perfusion pressure and regional myocardial performance of the right ventricular free wall was studied, in the presence or absence of right ventricular hypertension in 13 open-chest dogs. The right coronary artery was perfused through a shunt from a carotid artery. Regional systolic shortening of the right ventricular free wall was measured by means of a sonomicrometric technique at various levels of coronary perfusion pressure. Regional shortening was insensitive to coronary perfusion pressure or flow when it was above 31 mm Hg or 0.27 ml/min per g. Once coronary perfusion was below this critical level, regional shortening in both base to apex and circumferential orientations decreased linearly, depending on the degree of perfusion pressure. Despite the presence of a monoexponential relationship between coronary perfusion pressure or flow and regional shortening, a direct linear relation between perfusion pressure and flow was consistently noted, with or without pulmonary artery banding, suggesting that there is limited autoregulation of right coronary flow. The critical perfusion pressure for maintaining regional myocardial function of the right ventricle was highly dependent on the level of right ventricular systolic pressure (r = 0.64 - 0.72, P less than 0.05). Thus, right ventricular systolic pressure was one of the important determinants of regional wall motion during coronary underperfusion.     

Effect of graded reductions in regional coronary perfusion on regional and total cardiac function.

This study examines the effects of graded reduction in regional coronary perfusion and changes in arterial oxygen concentration upon regional myocardial function and left ventricular function. In 14 open chest dogs, the distal left anterior descending coronary artery was cannulated and perfused at different pressures with blood equilibrated with either 21 or 95 percent oxygen, and regional function in the perfused myocardial segment was determined by use of the pressure-length loop. The mass of perfused left ventricular myocardium was determined by injection of sodium fluorescein at a constant pressure of 100 mm Hg. Regional function decreased minimally as coronary perfusion pressure and flow were reduced to 50 to 65 mm Hg and 25 to 55 ml/min per 100 g, respectively. When pressure and flow were reduced below these critical ranges, regional function decreased sharply. Changes in left ventricular function were comparable but of lesser magnitude. The relations between regional function or left ventricular function and coronary perfusion were not affected by changing arterial oxygen concentration, except at the low range of coronary perfusion pressures (22 plus or minus 6 mm Hg), at which pressure regional function was significantly lower (P less than 0.025) in the experiments with 95 percent oxygen. Thus, the sensitivity of myocardial performance to a decrease in effective coronary perfusion pressure and flow is remarkably dependent upon whether pressure and flow are above a critical level.     

Coronary pressure-flow, pressure-function, and function-myocardial oxygen consumption relations in postischaemic myocardium.

STUDY OBJECTIVE--The aim was to study coronary pressure-flow, pressure-myocardial wall motion and myocardial wall motion-myocardial oxygen consumption relations in postischaemic myocardium with prolonged myocardial dysfunction (stunned myocardium) in comparison with normal myocardium. DESIGN--Regional myocardial wall thickening was measured with ultrasonic crystals, and postischaemic myocardial dysfunction was achieved by occlusion of a carotid-left anterior descending coronary artery bypass (15 min) and reperfusion (30 min). Coronary perfusion pressure was decreased in 10 mm Hg steps by constricting the bypass before and after producing postischaemic myocardial dysfunction. At each constriction step, coronary flow, regional wall thickening, and regional myocardial oxygen consumption in the area perfused by the left anterior descending artery were measured. EXPERIMENTAL MATERIAL--12 anaesthetised open chest mongrel dogs, weighing 12-16 kg, were studied. MEASUREMENTS AND MAIN RESULTS--At the basal level, myocardial wall thickening of postischaemic myocardium was depressed compared to normal myocardium, at 18.5(SD 8.9)% v 1.3(7.1)%, p less than 0.01. With coronary stenosis, wall thickening gradually decreased at a coronary pressure below 60 mm Hg in normal myocardium, but remained unchanged until mean coronary pressure was reduced to 50 mm Hg in postischaemic myocardium. Myocardial wall thickening of postischaemic myocardium was always more depressed than normal myocardium. At any level of coronary pressure, coronary flow in postischaemic myocardium was not different from normal myocardium. There was no difference in regional myocardial oxygen consumption between normal and postischaemic myocardium at any level of coronary pressure. However, regional myocardial oxygen consumption in postischaemic myocardium was higher than in normal myocardium performing similar levels of myocardial wall thickening. CONCLUSION--The coronary pressure-function relation but not the pressure-flow relation changed in postischaemic myocardium after a 15 min coronary occlusion. Regional myocardial oxygen consumption was relatively increased in postischaemic myocardium.     

Effect of elevations of coronary artery partial pressure of carbon dioxide (PCO2) on coronary blood flow

This study was designed to examine the effect of increases in the partial pressure of carbon dioxide (PCO2) in coronary artery blood on coronary blood flow, coronary reactive hyperemia and the coronary response to intracoronary adenosine administration. The left anterior descending coronary artery was cannulated and perfused over a wide range of perfusion pressure (P) and flow (F) with blood equilibrated with 0 to 40% carbon dioxide in 16 open chest dogs. Increases in coronary artery PCO2 from 20 +/- 2 to 93 +/- 8 to 211 +/- 22 mm Hg (mean +/- SEM) increased the coronary flow from 28 +/- 3 to 68 +/- 16 to 87 +/- 22 ml/min, respectively, at a perfusion pressure of 60 mm Hg and from 49 +/- 6 to 139 +/- 30 to 206 +/- 48 ml/min, respectively, at a perfusion pressure of 100 mm Hg. Coronary reactive hyperemia following a 30 second coronary perfusion line occlusion and the response to an intracoronary bolus of adenosine (60 micrograms) were prominent at a low PCO2 but absent at a high PCO2. Beta-adrenergic blockade did not abolish the increase in coronary flow that occurred at increased PCO2. Thus, progressive elevations of regional coronary PCO2 produced substantial increases in coronary blood flow and maximal or near maximal coronary vasodilation.     

The effect of coronary artery lesions on the relationship between coronary perfusion pressure and myocardial blood flow during cardiopulmonary resuscitation in pigs

In subjects without coronary disease, coronary perfusion pressure generated with closed-chest cardiopulmonary resuscitation (CPR) bears a direct relationship to myocardial blood flow. The effect of coronary lesions on this relationship was studied in an experimental porcine model not requiring thoracotomy. Coronary stenoses (a 50% reduction in coronary cross-sectional area) or total coronary occlusions were created by percutaneous, transarterial catheter placement of a Teflon cylinder in the left anterior descending artery of 21 swine (30 to 60 kg). Coronary perfusion pressure, defined as the aortic diastolic pressure minus right atrial diastolic pressure, was correlated with myocardial blood flow measured with nonradioactive, colored microspheres during external chest compression CPR. Complete occlusion of the left anterior coronary artery resulted in essentially no CPR-generated blood flow to the anterior myocardium distal to the site of occlusion. Coronary perfusion pressure showed a positive correlation with myocardial blood flow above the area of occlusion (r = 0.783; p less than 0.01) but did not correlate with myocardial blood flow below the occlusion site (r = 0.239). In the presence of a patent coronary artery stenosis, coronary perfusion pressure correlated with myocardial blood flow both above (r = 0.841; p less than 0.001) and below (r = 0.508; p less than 0.05) the stenosis. During closed-chest CPR producing coronary perfusion pressures between 30 and 60 mm Hg, anterior myocardial blood flow was 109 +/- 16 ml/min/100 gm above a patent stenosis and 66 +/- 13 ml/min/100 gm below the stenosis (p less than 0.005). Over a wide range of coronary perfusion pressures, myocardial blood flow below a coronary lesion was significantly less than that above the lesion. Coronary occlusions and stenoses can substantially affect the amount of CPR-generated coronary perfusion pressure needed to produce distal myocardial blood flow.     

Effects of nifedipine on coronary reactive and exercise induced hyperaemia

The effects of nifedipine on coronary vasodilation were studied during reactive hyperaemia after a transient coronary occlusion and during active hyperaemia associated with graded treadmill exercise. Studies were performed in 10 chronically instrumented dogs in which left circumflex coronary artery flow was measured with an electromagnetic flowmeter and myocardial oxygen extraction was determined from indwelling aortic and coronary sinus catheters. Thirty minutes after administration of nifedipine (10 micrograms.kg-1 iv), when coronary blood flow, arterial pressure, and heart rate had returned to control values, the vasodilatation following a 10 s coronary occlusion was significantly blunted, so that reactive hyperaemia blood flow debt repayment (mean(SEM)) was reduced from 387(39)% during control conditions to 270(33)% after nifedipine (p less than 0.05). In contrast, nifedipine did not alter the coronary vasodilatation that occurred in response to graded treadmill exercise so that the increase in coronary blood flow during exercise was not different from the control response. Thus, although nifedipine blunted ischaemic coronary vasodilatation during reactive hyperaemia, it did not alter coronary vasodilatation during active hyperaemia resulting from physiological increases of myocardial oxygen consumption.     

Coronary hemodynamics and subendocardial perfusion distal to stenoses

We compared distal coronary hemodynamics and regional myocardial perfusion in anesthetized dogs in the presence of a single or two coronary artery stenoses in series. After application of either a single or two stenoses on the left anterior descending coronary artery, regional myocardial blood flow was measured with radioactive microspheres. Moderate degrees of single-vessel stenosis (no change in resting coronary blood flow but reduction in reactive hyperemic response of 70%) resulted in no significant change in regional myocardial perfusion at rest despite a pressure drop across the stenosis of 24 +/- 3 mm Hg. When two such stenoses were applied in series, there was a 91% decrease in reactive hyperemia, a significant reduction in resting diastolic coronary blood flow and a 51 +/- 7 mm Hg pressure drop across the two stenoses. Alone, each stenosis produced no change in regional myocardial perfusion; however, together the two stenoses resulted in a significant decrease in subendocardial blood flow and a redistribution of transmural perfusion within the ischemic zone favoring the subepicardium (endo/epi from 0.95 +/- 0.03 to 0.72 +/- 0.03). The results indicate that whereas resting subendocardial perfusion is not significantly affected by moderate degrees of a single coronary artery stenosis, multiple stenoses of the same severity may dramatically reduce subendocardial perfusion.     

Regional myocardial function is not affected by severe coronary depressurization provided coronary blood flow is maintained

It has been suggested that vasodilation distal to a stenosis may cause a profound decrease in perfusion pressure and adversely affect regional left ventricular function. This phenomenon could explain the clinical concept of reversal of regional dysfunction by coronary revascularization. To evaluate the hypothesis that regional myocardial function parallels regional coronary blood pressure in the absence of changes in coronary flow, dogs chronically instrumented with left circumflex coronary artery flow probes, cuff occluders, pressure catheters and segmental function sonomicrometers were studied. By decreasing regional coronary vascular resistance with selective intracoronary dipyridamole and controlling blood flow with a proximal coronary cuff occluder, the mean left circumflex artery pressure was reduced from 83 +/- 3 to 38 +/- 2 mm Hg while circumflex coronary blood flow was maintained constant. Regional contractile function as measured by circumflex sonomicrometers was unchanged at constant circumflex subendocardial blood flow as measured by radioactive microspheres. These findings suggest that regional contractile function is dependent on subendocardial blood flow and is independent of coronary perfusion pressure.     

Effects of prindolol on isoproterenol-induced subendocardial ischaemia in dogs with multiple chronic coronary artery occlusion.

Multiple chronic coronary artery occlusions were produced in dogs by implantation of ameroid rings on the circumflex branches of the left and right coronary artery. Sixty-five per cent of the animals survived. Seventy-seven per cent of the remaining animals had no detectable myocardial infarction. Myocardial blood flow distribution was studied 4 weeks after operation using the tracer microsphere technique. During control conditions myocardial blood flow was homogeneously distributed within the left ventricle. In one group of dogs, regional dilatory capacity was tested by intravenous infusion of dipyridamole. Four compartments of myocardial blood flow were found. The collateral dependent subendocardium with 114 ml/min-100 g-1 was the lowest perfusion rate. In another group of dogs myocardial blood flow distribution was examined during isoproterenol infusion and after beta-blockade with prindolol during continuous isoproterenol infusion. During isoproterenol infusion, a nonhomogeneous blood flow pattern was found when the heart rate increased to 200/min together with a slight fall in diastolic perfusion pressure. Under these conditions, the flow to the collateral dependent subendocardium was severely diminished, while the flow to the areas perfused by normal coronary arteries increased, reflecting compensatory vasodilation. After beta-blockade with prindolol 0.1 mg/kg, the myocardial blood flow distribution was also nonhomogeneous but in the opposite direction: the collateral dependent subendocardium was now the best perfused compartment. The flow to the areas perfused by normal coronary arteries decreased due to the reduced oxygen requirements, while the collateral dependent subendocardium remained maximally dilated. This phenomenon was explained as a postischaemic reactive hyperaemic response to the isoproterenol-induced ischaemia in the collateral dependent subendocardium.     

Mechanism of attenuated pressure-flow autoregulation in right coronary circulation of dogs

Right coronary autoregulation was assessed in 14 open-chest, anesthetized dogs. In Group 1 (n = 5), the left common and right coronary arteries were cannulated and perfused independently. As coronary perfusion pressures varied simultaneously between 70 and 120 mm Hg, right coronary blood flow changed by 48%, whereas left coronary flow changed by 13%. In this pressure range, the autoregulatory closed-loop gain of the right coronary circulation averaged 0.37 +/- 0.01, reflecting a modest autoregulatory capability but significantly less than that of the left coronary circulation, 0.78 +/- 0.08. In Group 2 (n = 9), only the right coronary artery was perfused, and right coronary venous blood was collected for determining arteriovenous oxygen extraction. Autoregulatory gain was similar to that of Group 1, indicating that collateral flow associated with intercoronary pressure gradients does not mask right coronary autoregulation. Right ventricular myocardial oxygen consumption varied directly with perfusion pressure, ranging from 7.1 +/- 1.0 to 2.9 +/- 0.8 ml O2/min/100 g as pressure was reduced from 160 to 40 mm Hg. Thus, right coronary autoregulation is masked by an opposing change in oxygen demand. When right ventricular oxygen consumption was altered by pacing, a linear flow-oxygen consumption relationship was observed (8.2 +/- 0.4 ml/min/100 g per ml O2/min/100 g). Subtraction of flows associated with pressure-induced changes in metabolism revealed a potential autoregulatory capability of the right coronary circulation similar to that manifested by the left coronary circulation.     

Intracoronary endothelin-1 increases coronary retrograde pressure by constricting arterioles

STUDY OBJECTIVE--The aim was to determine the site of coronary vasoconstriction induced by endothelin, by investigating the response in terms of retrograde pressure and reactive hyperaemia. EXPERIMENTAL MATERIAL--Twelve anaesthetised mongrel dogs, 12-14 kg, were used for the studies. DESIGN--The left anterior descending coronary artery was cannulated and perfused with blood through an extracorporeal bypass. The effects of intracoronary endothelin-1 (1-500 pmol) on coronary blood flow, coronary flow reserve (the peak reactive flow and the repayment after 15 s coronary occlusion), and retrograde coronary pressure during coronary occlusion were studied (n = 7). The retrograde coronary flow was collected from the bypass at each dose (n = 5). MEASUREMENTS AND MAIN RESULTS--At doses of greater than 20 pmol the coronary flow decreased dose dependently and reached almost zero flow at 500 pmol. The coronary flow reserve also decreased; however, the retrograde pressure was raised dose dependently at doses of greater than 10 pmol. At a dose of 500 pmol, the retrograde pressure was increased to 61 mm Hg [82(SEM 12)% of the coronary perfusion pressure]. Retrograde flow remained unchanged throughout the experiment. CONCLUSIONS--The endothelin-1 induced rise in retrograde pressure is in accordance with a dose dependent reduction in coronary flow reserve, and collateral flow was not augmented by endothelin. It is concluded that the effect of endothelin-1 on coronary circulation in situ was mainly due to the constriction of small resistant vessels.     

Effect of coronary stenosis on myocardial blood flow during exercise in the chronically pressure-overloaded hypertrophied left ventricle

This study was performed to determine if a coronary artery stenosis would result in more-severe perfusion abnormalities in hypertrophied compared with normal canine hearts during exercise. Studies were performed in eight normal control dogs and in seven adult dogs in which a 67% increase in left ventricular mass wa produced by banding the ascending aorta at 9 weeks of age. Myocardial blood flow was measured by the microsphere method during treadmill exercise in the presence of a coronary artery stenosis that decreased distal coronary perfusion pressure to 55 or 42 mm Hg. At a coronary pressure of 55 mm Hg, mean myocardial blood flow was decreased by 23 +/- 5% in normal control dogs but was decreased by 53 +/- 10% in dogs with left ventricular hypertrophy (LVH) (p less than 0.05, comparing normal vs. LVH dogs). Similarly, at a coronary pressure of 42 mm Hg, mean blood flow was decreased by 53 +/- 6% below control in normal dogs but was decreased by 76 +/- 5% below control values in dogs with LVH (p less than 0.01, comparing normal vs. LVH dogs). In both groups of dogs, the stenosis caused a gradient of hypoperfusion, worsening from epicardium to endocardium. However, for each level of stenosis, subendocardial blood flow and the ratio of subendocardial to subepicardial blood flow was less in LVH than in normal canine hearts. These findings demonstrate that the presence of LVH secondary to long-term pressure overload is associated with an increased vulnerability to myocardial hypoperfusion during exercise in the presence of a coronary artery stenosis.     

Effect of age on coronary circulation after imposition of pressure-overload in rats.

We examined the effects of pressure overload on coronary circulation in young adult (7 months old) and old rats (18 months old). Four weeks after the ascending aorta was banded, in vivo left ventricular pressure was measured to estimate the degree of pressure load. In the two age groups, similar increases in peak left ventricular pressure were observed (113 +/- 7 mm Hg in sham-operated rats versus 160 +/- 11 mm Hg in banded rats of the young adult group; 103 +/- 7 mm Hg in sham-operated rats versus 156 +/- 11 mm Hg in banded rats of the old group). After isolating the hearts, they were perfused with Tyrode's solution containing bovine red blood cells and albumin. Resting coronary perfusion pressure-flow relations and reactive hyperemic response after a 40-second ischemia were obtained under beating but nonworking conditions. In young adult banded rats, significant myocardial hypertrophy was observed at the organ level (124% of controls in left ventricular dry weight/body weight ratio; 119% in left ventricular dry weight/tibial length ratio) and at the cell level. Minimal coronary vascular resistance obtained by the perfusion pressure-peak flow relation during reactive hyperemia increased to 150% of controls, and coronary flow reserve decreased significantly. In contrast, myocardial hypertrophy was not observed at the organ or cell level in old banded rats. However, minimal coronary vascular resistance increased, and flow reserve decreased significantly. Thus, pressure overload with coronary arterial hypertension caused abnormalities of the coronary circulation in old subjects even in the absence of myocardial hypertrophy.     

Role of adenosine in coronary blood flow regulation after reductions in perfusion pressure

We employed intracoronary infusion of adenosine deaminase to test the hypothesis that endogenous adenosine contributes to regulation of coronary blood flow following acute reductions in coronary artery pressure. In 16 closed-chest anesthetized dogs, we perfused the left circumflex coronary artery from a pressurized arterial reservoir and measured coronary blood flow following changes in perfusion pressure before and 10 minutes after the start of intracoronary adenosine deaminase, 5 U/min per kg body weight. Parallel studies showed that this dose of enzyme resulted in cardiac lymph adenosine deaminase concentrations of 3.2 +/- 0.4 U/ml. Adenosine deaminase abolished the vasodilator response to intracoronary adenosine, 4 and 8 micrograms, but had no effect on the vasodilator response to intracoronary papaverine, 200 and 300 micrograms, demonstrating enzyme efficacy and specificity. Additional experiments demonstrated that adenosine deaminase reversibly attenuated myocardial reactive hyperemia following 5- and 10-second coronary occlusions by 30% (P less than 0.05), evidence that the infused enzyme effectively degraded endogenous adenosine. However, adenosine deaminase did not alter the time course for coronary autoregulation or the steady state autoregulatory flow response over the pressure range between 125 and 75 mm Hg. Further, adenosine deaminase did not alter steady state coronary flow when perfusion pressure was reduced below the range for effective autoregulation (60-40 mm Hg). Such results show that adenosine is not essential for either coronary autoregulation or for the maintenance of coronary vasodilation when autoregulatory vasodilator reserve is expended.     

Compensatory regional contraction following coronary artery occlusion depends on subendocardial hyperaemia and hyperkinesis.

The effects of circumflex coronary artery occlusion on regional myocardial performance and blood flow in the left ventricular anterior wall was studied, using 16 thoracotomized pentobarbital-anaesthetized cats. Two pairs of ultrasonic crystals were placed in the midwall; one segment (longitudinal) parallel to the subendocardial fibres, the other (circumferential) being aligned to the fibres of the outer half-layer. A shunt line from the right subclavian artery to the main left coronary artery was unrestricted in eight cats (Group A) and clamped in another eight cats (Group B) until coronary perfusion pressure was clearly reduced with only a minor reduction in shunt flow, but without changes in global cardiac function. After circumflex coronary occlusion hyperkinesis was most pronounced in segments parallel to subendocardial fibres (longitudinal), also validated as a marked leftward shift in the end-systolic pressure-length relation of these segments. Such a shift may indicate decreased regional afterloading along the cardiac major axis. Hyperkinesis of longitudinal segments was attenuated in Group B where a fixed shunt stenosis hampered subendocardial and mid-myocardial hyperaemia. The lesser hyperkinesis of Group B was associated with decreased left ventricular systolic pressure and cardiac output. Thus, impaired compensatory contraction outside an acute ischaemic region was produced by a significant coronary stenosis which precluded the subendocardial hyperaemia and hyperkinesis of that region.     

Evaluation of coronary collateral development by regional myocardial function and reactive hyperaemia

The development of collateral vessels was induced by repeated brief left circumflex coronary artery occlusions in 11 conscious dogs. Subendocardial segment shortening in the central ischaemic area and the ischaemic marginal area and transmural wall thickening in the centre of the ischaemic area were measured together with circumflex coronary flow. Changes in regional myocardial function and reactive hyperaemia were determined daily. The rate of recovery of myocardial function after collateralisation was almost identical in both regions. Before myocardial contractility was restored reactive hyperaemia was greatly attenuated. These data strongly suggest that collateral flow is distributed uniformly over the ischaemic bed and that substantial areas of myocardial tissue at risk are salvaged from ischaemia as a result of effective collateral circulation.     

Contrast echocardiography during coronary arteriography in humans: perfusion and anatomic studies

In humans, the physiologic relation between myocardial blood flow and epicardial coronary artery anatomy remains poorly defined. With the recent development of sonicated microbubble contrast agents, it is now possible to use contrast echocardiography to assess myocardial perfusion and to correlate blood flow with angiographically identified coronary artery anatomy. The purpose of the current study was to determine myocardial perfusion patterns in patients without significant coronary artery disease. The results may be used as a reference to analyze myocardial blood flow in patients with coronary artery disease. Sonicated meglumine sodium diatrizoate solution (Renografin-76), which contains microbubbles measuring 4.5 +/- 2.8 micrograms in diameter by laser analysis, was used as the echocardiographic contrast agent during elective coronary arterriography in 14 patients without significant coronary artery disease. Patients received intracoronary injections of 1.5 to 2 ml of sonicated Renografin-76 without complications. Perfusion characteristics were studied by visual assessment of the two-dimensional echocardiographic images obtained after individual injections. In patients found to be free of significant coronary artery disease by arteriography, the left coronary system always supplied the anteroseptal, anterior, anterolateral and posterior regions of the left ventricle at the mid-papillary, cross-sectional level. The right coronary artery system perfused the inferior and inferoseptal regions in 89% of the patients identified with a right dominant system. The anterolateral papillary muscle was perfused from the left coronary system in all cases. The posteromedial papillary muscle was perfused from the left coronary system in 58% of the patients and from the right system in 42% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vagal chemoreflex coronary vasodilation evoked by stimulating pulmonary C-fibers in dogs

We performed experiments on anesthetized, open-chest dogs to determine whether the pulmonary chemoreflex (bradycardia and systemic hypotension) evoked by stimulating pulmonary C-fibers also involves reflex changes in coronary vascular resistance. We perfused the circumflex coronary artery at constant pressure (usually 100 mm Hg) and recorded mean circumflex blood flow. Stimulation of pulmonary C-fibers by right atrial injection of capsaicin (10 micrograms/kg) decreased arterial blood pressure and heart rate and increased circumflex blood flow by 32-109% (P less than 0.001). Circumflex blood flow also increased, by 26-100% (P less than 0.001), when heart rate was kept constant by pacing. Coronary vasodilation was not secondary to the reflex decrease in arterial blood pressure. Injecting capsaicin (10 micrograms/kg) into the left atrium did not increase circumflex blood flow. Reflex coronary vasodilation could still be evoked when myelinated nerve fibers were blocked selectively by cooling the cervical vagus nerves to 7-8 degrees C but was abolished by cooling to 0 degrees C, by cutting the pulmonary vagal branches, or by giving atropine. Reducing coronary perfusion pressure shifted the stimulus (dose of capsaicin)-response (increase in coronary blood flow) curve to the right, but, even at low perfusion pressures, significant reflex vasodilation still occurred. Regional (transmural) distribution of myocardial blood flow was measured by the microsphere technique at various perfusion pressures. The endocardial:epicardial blood flow ratio decreased significantly as perfusion pressure was reduced, but was not altered by right atrial injection of capsaicin at any perfusion pressure. Our results indicate that stimulation of pulmonary C-fibers triggers reflex cholinergic vasodilation in all layers of the myocardium.     

Normalization of impaired coronary circulation in hypertrophied rat hearts

We tested the hypothesis that impaired coronary autoregulation, decreased flow reserve, and diminished reactive hyperemic response in hypertrophied hearts with coronary arterial hypertension may be reversible after relief of pressure overload. In 4-week ascending aortic banded rats, in vivo peak systolic left ventricular pressure increased to 178 +/- 8 mm Hg (103 +/- 6 mm Hg in sham-operated control group). This increased pressure produced myocardial hypertrophy, and the left ventricular weight/body weight ratio was 46% above that of the control group. After the rats were killed, the coronary perfusion pressure-flow relations were obtained during resting conditions and maximal vasodilation after a 40-second period of ischemia in beating but nonworking isolated hearts perfused with Tyrode's solution with bovine red blood cells and albumin. In hearts from control rats, coronary autoregulation (i.e., a slight decrease in flow with reduction of pressure) was observed in the range of 50-100 mm Hg of perfusion pressure. A pronounced reactive hyperemic response was observed: a peak flow/resting flow ratio of 2.9 +/- 0.1 and a repayment ratio of 1.7 +/- 0.2 at 100 mm Hg of perfusion pressure. In hearts of banded rats the resting pressure-flow relation was rectilinear in the range of 25-175 mm Hg of perfusion pressure. Flow reserve and the time of reactive hyperemia to one half peak flow decreased at 50, 100, and 150 mm Hg of perfusion pressure compared with values in control rat hearts. Four weeks after debanding, peak systolic left ventricular pressure and cardiac hypertrophy had normalized. The impaired autoregulation, decreased flow reserve, and diminished reactive hyperemic response had completely reversed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nitric oxide contributes to oxygen demand-supply balance in hypoperfused right ventricle

OBJECTIVE: The present study examined the role of nitric oxide (NO) in oxygen demand-supply balance in hypoperfused canine right ventricular myocardium. METHODS: The right coronary artery of anesthetized, open-chest dogs was perfused at pressures of 80, 60, and 40 mm Hg, and right ventricular myocardial oxygen consumption, right coronary blood flow and other hemodynamic and cardiac function variables were measured. Right ventricular mechanical function was indexed as the product of heart rate x peak right ventricular systolic pressure x right ventricular dP/dt(max). NO synthesis blocker N(omega)-nitro-L-arginine methyl ester (L-NAME, 150 mug/min) was infused into the right coronary artery to block NO synthesis. RESULTS: Neither hypoperfusion nor L-NAME altered right ventricular function. Right ventricular myocardial oxygen consumption fell with coronary perfusion pressure, but less steeply after L-NAME, and at all perfusion pressures was elevated above control. The increase in myocardial oxygen consumption in the absence of NO was met by increased oxygen extraction and by non-NO dependent vasodilation, but the relationship between flow and oxygen consumption was displaced downward after L-NAME. As right coronary perfusion pressure was reduced, the relationship between right ventricular oxygen consumption and right coronary venous PO(2) became steeper after L-NAME, and right coronary venous PO(2) was significantly reduced. CONCLUSIONS: During right coronary hypoperfusion, right ventricular function is well maintained, but myocardial oxygen consumption falls, reflecting an increase in oxygen utilization efficiency. NO contributes to this adaptation to hypoperfusion by restraining myocardial oxygen consumption, and by promoting coronary vasodilation with less severe reduction in myocardial PO(2). NO has an important role in right ventricular oxygen demand-supply balance when right coronary perfusion pressure is reduced.