Differential effects of isoflurane on regional right and left ventricular performances, and on coronary, systemic, and pulmonary hemodynamics in the dog

The effects of isoflurane-induced hypotension to mean aortic pressures of 70 and 55 mmHg on global and regional right (RV) and left (LV) ventricular performance (ultrasonic dimension technique), and on coronary, systemic, and pulmonary hemodynamics (electromagnetic flow probes) were studied in 12 open-chest dogs anesthetized and paralyzed by continuous infusions of fentanyl and pancuronium. Isoflurane caused dose-dependent decreases in LV and RV dP/dt, and in myocardial segment shortening in the presence of unchanged heart rate, unchanged or increased (RV) preload, and unchanged (RV) or decreased (LV) afterload. RV and LV functions were affected differently: at a mean aortic pressure of 70 mmHg (mean inspired isoflurane 1.2%), RV end diastolic dimensions and pressure remained unchanged, whereas those of the LV decreased. At a mean aortic pressure of 55 mmHg (mean inspired isoflurane 1.8%), RV end diastolic dimensions and pressure increased above control, whereas those of the LV remained unchanged. Within the RV, inflow and outflow tract were affected quantitatively similarly, but dyssynchrony developed in four animals. Isoflurane caused dose-dependent decreases in coronary and systemic vascular resistances, but no change in pulmonary vascular resistance. At the lower concentration of isoflurane, coronary blood flow did not fall despite decreased LV and RV dP/dt, unchanged heart rate, unchanged or decreased preload, and unchanged or reduced afterload. The data indicate that isoflurane is a myocardial depressant and a potent coronary vasodilator. At both concentrations, LV function was better preserved than RV function, most likely due to the different effects of isoflurane on RV (unchanged) and LV (reduced) afterload.     

CARDIOVASCULAR EFFECTS OF DILTIAZEM IN THE DOG

The effects of two bolus injections (0.2 mg kg^–1) andtwo infusion rates (0.2 mg min^–1 and 0.4 mg min^–1)ofdiltiazem on global and regional left (LV) and right ventricular(RV) performance (ultrasonic dimension technique), on coronary(electromagnetic flow meters) and systemic haemodynamics, andon electrophysiology (PR, QRS, QT_C intervals) were studied ineight open-chest dogs anaesthetized with droperidol and fentanyl.The two bolus injections of diltiazem resulted in plasma concentrationsof 688 ± 115 and 650 ± 85 ng ml^–1 (means± SE), respectively, and caused substantial decreasesin systemic and coronary vascular resistances, and in aorticpressure, and increases in LV segment shortening, stroke volumeand aortic flow. Electro -physiological variables were littleaffected. At the low infusion rate (plasma concentration 140± 23 ng ml^–1) coronary and systemic vaso-dilatationoccurred, but global and regional RV and LV performance werelittle affected. PR interval increased by 15%. At the higherinfusion rate (plasma concentration 282 ± 33 ng ml^–1)coronary and systemic vasodilatation were maintained. Aorticpressure decreased slightly. Whereas LV end-diastolic and end-systolicdimensions remained unchanged, they increased in the RV. Inaddition, the PR interval increased by 35%, and three animalsdeveloped atrio-ventricular block type I. The data indicatethat diltiazem is a potent coronary and systemic vasodilatorwith little effect on global RV and L V performance. However,at a higher infusion rate RV dimensions clearly tend to increase,and conduction abnormalities develop.     

Influence of diltiazem on cardiovascular function and coronary hemodynamics during isoflurane anesthesia in the dog: correlation with plasma diltiazem levels

Diltiazem was administered to dogs by intravenous infusion to achieve plasma levels of 47 +/- 3 (n = 7), 148 +/- 12 (n = 8), 263 +/- 10 (n = 8), and 379 +/- 43 (n = 8) ng X ml-1, to evaluate the effects of diltiazem on cardiovascular function and coronary hemodynamics, when given in the presence of anesthetic concentrations of isoflurane. Plasma level related prolongation of the PR interval of the electrocardiogram was the most prominent effect observed, with development of 2 degrees heart block or junctional rhythms in several of the animals at the two higher plasma levels. Mean arterial pressure, transiently decreased after the loading dose in all groups, was no different from control values after 30 min of infusion. Left ventricular dP/dt was mildly decreased at the three highest plasma levels, whereas right and left heart filling pressures were increased at the two highest plasma levels. Cardiac index and systemic vascular resistance were unchanged. No changes were observed in coronary sinus blood flow, coronary vascular resistance, myocardial oxygen uptake, myocardial lactate extraction, or circulating epinephrine or norepinephrine levels in any of the groups. In the presence of anesthetic concentrations of isoflurane, over the range of plasma levels investigated in this study, the vasodilating properties of diltiazem were not observed, yet conduction effects were prominent and decreases in left ventricular performance occurred. No untoward effects on global myocardial metabolism were detected under these conditions.     

Combined effects of verapamil and isoflurane on coronary blood flow and myocardial metabolism in the dog

The effects of three different plasma levels of verapamil on coronary hemodynamics and myocardial metabolism in the presence of 1.61 +/- 0.05% end-tidal concentration of isoflurane (mean +/- SEM) were studied in a canine model, using a thermodilution coronary sinus catheter to measure coronary sinus blood flow and pressure and to provide coronary sinus plasma samples. A control group receiving only isoflurane was also studied (n = 6). Plasma arterial verapamil levels of 55 +/- 7 (n = 6); 134 +/- 7 (n = 10); and 301 +/- 37 ng X ml-1 (n = 5), were achieved by a loading dose followed by a continuous infusion for 30 min. The only changes with time in the isoflurane group were decreases in left ventricular maximum rate of tension development (dP/dt) and left ventricular stroke work index compared with control after 90 min without changes in myocardial oxygen balance. The low plasma verapamil level caused reductions in heart rate, mean and diastolic arterial pressure, and left ventricular dP/dt without changes in myocardial oxygen supply or myocardial metabolism. Intermediate verapamil concentrations produced a transient initial increase in heart rate and a reduction in stroke volume index. With the intermediate and the highest levels of verapamil, mean and diastolic arterial pressure, left ventricular dP/dt, and cardiac index were decreased. An increase in arterial norepinephrine plasma levels was seen in the intermediate and the highest levels of verapamil; however, a transient coronary vasodilation occurred without changes in myocardial oxygen balance. Significant prolongation of the PR interval was observed in all verapamil groups, with second or third degree heart block in some of the higher-dose animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Control of intraoperative hypertension with isoflurane in patients with coronary artery disease: effects on regional myocardial blood flow and metabolism

The effect of isoflurane on regional myocardial metabolism and blood flow, when used as an adjunct to fentanyl-nitrous oxide anesthesia, to control intraoperative hypertension was investigated. Twenty-two patients with two- or three-vessel coronary artery disease with an ejection fraction greater than 0.5 and on beta-blockers up to the morning of surgery were studied during elective coronary artery by-pass grafting. Systemic and pulmonary hemodynamics, and regional (great cardiac vein, GCVF) myocardial blood flow and myocardial metabolic parameters were measured. In 10 patients, both GCVF and global (coronary sinus, CSF) myocardial blood flows were recorded. Measurements were made 1) after induction of anesthesia but prior to skin incision, 2) during sternotomy, and 3) during isoflurane administration after its use to reduce arterial pressure to the presternotomy level. The increase in systemic arterial pressure during sternotomy was due to an increase in systemic vascular resistance accompanied by increases in heart rate, pulmonary capillary wedge pressure, (PCWP) regional myocardial oxygen consumption and extraction, GCVF and total coronary vascular resistance. Isoflurane reduced systemic arterial pressure but not PCWP, to presternotomy levels within 6.9 +/- 0.7 minutes at an end-tidal concentration of 1.5 +/- 0.2%. Isoflurane induced a pronounced systemic and coronary vasodilatation and increases in cardiac index, heart rate and regional myocardial oxygen extraction while the GCVF/CSF ratio remained unchanged. While mean regional--MLE% values were not effected by sternotomy, in two patients myocardial lactate production was seen during sternotomy but not during isoflurane. In another two patients, isoflurane induced lactate production.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma diltiazem levels, cardiovascular function, and coronary hemodynamics during enflurane anesthesia in the dog

Diltiazem was administered to dogs by an intravenous infusion protocol, which resulted in plasma levels of 71 +/- 6 (n = 7), 139 +/- 9 (n = 7), 353 +/- 33 (n = 10), and 1064 +/- 143 (n = 6) ng/ml, to evaluate the effects of diltiazem on cardiovascular function and coronary hemodynamics in the presence of anesthetic concentrations of enflurane. An additional group of six dogs received enflurane only. The only changes observed with enflurane alone were a decrease in left ventricular (LV) dP/dt, cardiac index (CI), and coronary blood flow 60 min after the baseline measurements were made. In all of the diltiazem groups, plasma level-related prolongation of the PR interval of the electrocardiogram was observed, with development of second degree heart block and junctional rhythms in animals at the two higher plasma levels. Mean arterial pressure and LV dP/dt decreased at the two higher diltiazem plasma levels after 30 min of infusion, and three of six dogs in the highest group had to be dropped from the study because of severe hypotension. The cardiac index was no different from enflurane alone with the three lower plasma diltiazem levels. No changes were observed in coronary sinus blood flow, coronary vascular resistance, myocardial oxygen uptake, or myocardial lactate extraction. Circulating norepinephrine levels were elevated in the two higher diltiazem groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of desflurane,isoflurane and halothane on regional tissue perfusion in dogs

The actions of desflurane, isoflurane and halothane on regional tissue perfusion were studied using radioactive microspheres in dogs chronically instrumented for measurement of arterial and left ventricular pressure, global (left ventricular dP/dtmax) and regional (percent segment shortening) contractile function, and diastolic coronary blood flow velocity. Systemic and coronary haemodynamics and regional tissue perfusion were measured in the conscious state and during anaesthesia with equihypotensive concentrations of desflurane, isoflurane, and halothane. All three volatile anaesthetics (P < 0.05) increased heart rate and decreased mean arterial pressure, left ventricular systolic pressure, and left ventricular dP/dtmax Myocardial perfusion was unchanged in subendocardial midmyocardial, and subepicardial regions by the administration of either dose of desflurane. No redistribution of intramyocardial blood flow (endo/epi ratio) was observed during desflurane anaesthesia. Although regional myocardial perfusion was reduced (P < 0.05) in a dose-related fashion by halothane and by isoflurane at high concentrations, redistribution of intramyocardial blood flow was not observed during halothane or isoflurane anaesthesia. All three volatile anaesthetics reduced blood flow to the renal cortex, but only desflurane produced a decrease in renal cortical vascular resistance. Hepatic blood flow decreased in response to halothane but not desflurane or isoflurane. Concomitant decreases in hepatic resistance were observed during administration of desflurane and isoflurane. Dose-related decreases in intestinal and skeletal muscle blood flow were observed during halothane and isoflurane but not desflurane anaesthesia. The results suggest that desflurane maintains myocardial, hepatic, intestinal, and skeletal muscle blood flow while halothane and isoflurane decrease regional tissue perfusion in these vascular beds to varying degrees during systemic hypotension in the chronically instrumented dog.     

Global and regional myocardial blood flow and metabolism during equipotent halothane and isoflurane anesthesia in patients with coronary artery disease

Global and regional myocardial blood flow and metabolism were examined in 20 patients with coronary artery disease before surgical stimulation. Half were anesthetized with halothane (0.8%) and half with isoflurane (1.2%). Coronary perfusion pressure decreased similarly in both groups. During halothane anesthesia coronary sinus blood flow, an index of global perfusion, decreased from an awake value of 129 +/- 7 to 97 +/- 7 ml/min (P less than 0.05), and great cardiac vein blood flow, an index of regional perfusion, decreased from 60 +/- 8 to 44 +/- 5 ml/min (P less than 0.05). In contrast, during isoflurane anesthesia global coronary blood flow increased from 131 +/- 13 to 153 +/- 16 ml/min (P less than 0.05), while regional blood flow decreased from 68 +/- 7 to 56 +/- 6 ml/min (P less than 0.05). Thus, the ratio of great cardiac vein blood flow to coronary sinus blood flow was unchanged during halothane anesthesia but decreased significantly during isoflurane. Neither global nor regional coronary vascular resistance was altered by halothane, whereas isoflurane decreased global coronary vascular resistance without affecting regional coronary vascular resistance. All patients receiving halothane had net myocardial lactate extraction. In the isoflurane group, four patients showed global lactate production and three regional lactate production. All patients demonstrating lactate production also developed electrocardiographic evidence of myocardial ischemia, which was not present before induction. The authors conclude that halothane is a preferable anesthetic to isoflurane in patients with coronary artery disease because the latter has the propensity to induce maldistribution of the coronary circulation and myocardial ischemia.     

Myocardial perfusion and right ventricular function.

Objective: Maximal right ventricular (RV) performance is influenced by left heart hemodynamics and hence coronary perfusion. We examined the role of myocardial perfusion of the right ventricle as potential determinant of maximal RV function. Materials and methods: In 6 canine isovolumic right heart preparations, incremental volumes were introduced into a high compliance RV balloon until RV failure occurred. Maximal RV developed pressure (RVDP) and maximal positive RV dP/dt were determined at a constant controlled left ventricular (LV) output of 2 l/min and at controlled mean arterial pressures of 50, 80 and 120 mmHg. Right coronary artery (RCA) flow was measured. Results: Maximal RVDP increased significantly with increasing mean arterial pressures (44.8+/-11.2 vs 57.2+/-15.5 vs 75.4+/-2.5 mmHg for systemic pressures of 50, 80 and 120 mmHg respectively, p < 0. 05). With increasing mean arterial pressures RCA flow increased significantly (33.1+/-11.0 vs 46.1+/-20.4 vs 79.6+/-35.3 ml/min). At the onset of RV failure, RCA blood flow significantly decreased in all preparations compared to the maximal flow in the RCA (1.9+/-1.0 vs 33.1+/-11.0 ml/min at 50 mmHg; 13.6+/-10.2 vs 46.1+/-20.4 ml at 80 mmHg and 18.7+/-8.0 vs 79.6+/-35.3 ml/min at 120 mmHg; p < 0.05). Conclusions: These results suggest that coronary perfusion is a major determinant of maximal RV function. The coronary artery driving pressure must be sufficient to avoid the onset of RV failure. Maintaining systemic pressure and hence RV myocardial blood flow may thus extend RV function.     

Transmural coronary vasodilator reserve and flow distribution in unanesthetized calves sojourning at 3500 m

Regional myocardial blood flow (MBF; 15-micron-diam radionuclide-labeled microspheres) was studied in six unanesthetized calves sojourning at 3500 m (PB = 500 mm Hg) for 53 +/- 2 days. These high-altitude (HA)-exposed calves were studied during chronic hypoxemia (PaO2 = 48 +/- 1 mm Hg), maximal coronary vasodilation, and during acute normoxemia (PaO2 = 91 +/- 1 mm Hg). Nine calves born and raised at sea level (SL) were also studied at matched PaO2 during chronic normoxemia, maximal coronary vasodilation, and acute hypoxemia to serve as control. Marked pulmonary hypertension and right ventricular (RV) hypertrophy were present in HA calves. Left ventricular (LV) MBF of HA calves during chronic hypoxemia (1.05 +/- 0.11 ml X min-1 X g-1) was similar to that of normoxemic SL calves (1.11 +/- 0.06 ml X min-1 X g-1) but MBF in their hypertrophied RV (1.65 +/- 0.21 ml X min-1 X g-1) exceeded that in normoxemic SL calves (0.47 +/- 0.06 ml X min-1 X g-1). More interesting was the finding that RV and LV MBF of HA calves did not change between chronic hypoxemia and acute normoxemia. By contrast, acute hypoxemia of a similar degree caused a dramatic increase in RV as well as LV MBF of SL calves. Minimal LV coronary vascular resistance was similar in the two groups of calves. This meant that functional cross-sectional area of LV coronary vascular bed was not altered in response to sojourn at HA. Minimal RV coronary vascular resistance of HA calves was also not different from that of SL calves. This means that functional cross-sectional area of the RV coronary vascular bed in HA calves increased proportionately with the increase in their RV mass.     

Myocardial circulatory and metabolic effects of isoflurane and sufentanil during coronary artery surgery

The global and regional coronary hemodynamic and myocardial metabolic effects of isoflurane administered intraoperatively as an adjunct to sufentanil were studied in seven of nine patients who experienced increased systemic arterial pressure while undergoing elective coronary artery bypass grafting. All patients were premedicated and maintained on their preoperative medications (beta-blockers, nitrates, Ca++ entry blockers) up to and including the morning of surgery. Systemic and pulmonary hemodynamics and global (coronary sinus, CS) and regional (great cardiac vein, GCV) coronary blood flows were measured, and blood samples were obtained for systemic and myocardial metabolic parameters: after induction with 30 mcg/kg of sufentanil and 0.12 mg/kg vecuronium (FIO2 1.0), but prior to incision (control); 5 min after sternotomy; and during ventilation with isoflurane-oxygen. Heart rate, cardiac output, stroke volume, and GCV/CS flow ratio did not change throughout the study. Neither global nor regional myocardial lactate production was detected in any patient at any time, and the electrocardiogram (lead II, V5) remained unchanged. In response to sternotomy, seven of nine patients experienced an increase in mean systemic arterial pressure of 20% or more (27 +/- 3% from control values), due to an elevation in systemic vascular resistance (30 +/- 5%). Coronary sinus (CS) and great cardiac vein (GCV) flows, as well as CS and GCV lactate extractions, were unchanged 5 min after sternotomy. Both global and regional myocardial oxygen extraction increased, while coronary venous oxygen content decreased. Isoflurane was administered in a dose that restored systemic arterial pressure to baseline values (inspired concentration 0.75-1.0%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Adenosine for controlled hypotension: systemic compared with intracoronary infusion in dogs.

We hypothesized that either through local myocardial or systemic effects, adenosine could be used to control hypotension during ischemia. Therefore, we compared the effects of systemic with intracoronary infusion of adenosine on myocardial hemodynamics and metabolism during ischemia in 27 dogs. Left anterior descending artery (LADa) flow was measured and the LADa constricted by a micrometer to restrict resting flow by 50%, 75%, and 100%. Adenosine was infused either systemically (n = 9), to maintain mean aortic pressure at 50-60 mm Hg, or directly into the LADa (n = 9), to create maximal coronary hyperperfusion; no adenosine was infused in the control group (n = 9). With systemic adenosine, during each constriction aortic pressure, left ventricular first derivative (LV dP/dt), and heart rate (HR) decreased: aortic pressure by 56.1% +/- 2.9% (mean +/- SEM), LV dP/dt by 36.2% +/- 2.2%, systemic resistance by 42.7% +/- 5%, and HR by 38.7% +/- 3% during 50% constriction (P less than 0.05 for each variable). Intracoronary adenosine decreased only aortic pressure, LV dP/dt, and HR, all to a lesser extent: aortic pressure by 5% +/- 2.8%, LV dP/dt by 15% +/- 1.2%, and HR by 4.6% +/- 1.7% (P less than 0.05, compared with systemic adenosine for each variable). With systemic adenosine only in the nonischemic area, regional myocardial blood flow increased and remained high, from 224.6 +/- 65.2 to 342 +/- 46.2 mL.min-1.100 g-1 during 50% constriction (P less than 0.05); with intracoronary adenosine, ischemic zone regional myocardial blood flow increased, but not consistently. In the ischemic area, O2 consumption was less with than without systemic adenosine; also, lactate flux production was less positive (-60.2 +/- 37.6 compared with 80.3 +/- 20.2 mmol.min-1.100 g-1 x 10(-3) during 50% constriction; P less than 0.05). Systemic infusion of adenosine during coronary hypoperfusion improves regional metabolism during ischemia and, thus, may mitigate myocardial ischemia. The mechanism by which systemic infusion improves metabolic status may be by decreases in both systemic pressure and systemic vascular resistance.     

Continuous cold blood cardioplegia improves myocardial protection: a prospective randomized study

BACKGROUND: To assess the influence on myocardial protection of the rate of infusion (continuous vs intermittent) of cold blood cardioplegia administered retrogradely during prolonged aortic cross-clamping. The end-points were ventricular performance and biochemical markers of ischemia. METHODS: Seventy patients undergoing myocardial revascularization for three-vessel disease were prospectively randomized to receive intermittent or continuous retrograde cold blood cardioplegia. Hemodynamic measurements were obtained using a rapid-response thermodilution catheter and included right ventricular ejection fraction, cardiac output, left and right ventricular stroke work index, and systemic and pulmonary vascular resistance. Blood samples were obtained from the coronary sinus before cross-clamp application and immediately after cross-clamp removal for determinations of lactate and hypoxanthine. RESULTS: The left ventricular stroke work index trend was significantly superior (p = 0.038) by repeated-measures analysis in continuous cardioplegia. Other hemodynamic measurements revealed a similar trend. The need for postoperative inotropic drugs support was reduced in continuous cardioplegia. The release of lactate in the coronary sinus after unclamping was 2.30 +/- 0.12 mmol/L after intermittent cardioplegia and 1.97 +/- 0.09 mmol/L after continuous cardioplegia (p = 0.036). The release of hypoxanthine was 20.47 +/- 2.74 micromol/L in intermittent cardioplegia and 11.77 +/- 0.69 micromol/L in continuous cardioplegia (p = 0.002). CONCLUSIONS: Continuous cold blood cardioplegia results in improved ventricular performance and reduced myocardial ischemia in comparison with intermittent administration.     

Comparison of the systemic and coronary hemodynamic actions of desflurane, isoflurane, halothane, and enflurane in the chronically instrumented dog

The systemic and coronary hemodynamic effects of desflurane were compared to those of isoflurane, halothane, and enflurane in chronically instrumented dogs. Since autonomic nervous system function may significantly influence the hemodynamic actions of anesthetics in vivo, a series of experiments also was performed in the presence of pharmacologic blockade of the autonomic nervous system. Eight groups comprising a total of 80 experiments were performed on 10 dogs instrumented for measurement of aortic and left ventricular pressure, the peak rate of increase of left ventricular pressure (dP/dt), subendocardial segment length, coronary blood flow velocity, and cardiac output. Systemic and coronary hemodynamics were recorded in the conscious state and after 30 min equilibration at 1.25 and 1.75 MAC desflurane, isoflurane, halothane, and enflurane. Desflurane (+79 +/- 12% change from control) produced greater increases in heart rate than did halothane (+44 +/- 12% change from control) or enflurane (+44 +/- 9% change from control) at 1.75 MAC. Desflurane preserved mean arterial pressure to a greater degree than did equianesthetic concentrations of isoflurane. This result was attributed to a smaller effect on peripheral vascular resistance as compared to isoflurane and greater preservation of myocardial contractility as evaluated by peak positive left ventricular dP/dt and the rate of increase of ventricular pressure at 50 mmHg (dP/dt50) compared to other volatile anesthetics. Increases in diastolic coronary blood flow velocity (+19 +/- 6 and +35 +/- 12% change from control at 1.75 MAC, respectively) and concomitant decreases in diastolic coronary vascular resistance (-41 +/- 12 and -58 +/- 6% change from control at 1.75 MAC, respectively) were produced by desflurane and isoflurane. In the presence of autonomic nervous system blockade, the actions of desflurane and isoflurane were nearly identical with the exception of coronary vasodilation. After autonomic nervous system blockade, isoflurane increased coronary blood flow velocity, but desflurane did not. Furthermore, both desflurane and isoflurane continued to produce less depression of myocardial contractility than did halothane and enflurane. In summary, at equianesthetic concentrations, desflurane and isoflurane produced similar hemodynamic effects; however, in the absence of drugs that inhibit autonomic reflexes, desflurane had less negative inotropic activity and produced less decrease in arterial pressure. The coronary vasodilator actions of desflurane and isoflurane within the limitations of this model were not similar. When the increase in heart rate and rate-pressure product produced by desflurane were prevented in dogs with autonomic nervous system blockade, desflurane produced no change in coronary blood flow velocity.     

Identification and control of noncoronary collateral blood flow

To identify the source of noncoronary collateral myocardial blood flow and to establish methods to control it during induced ischemia, 29 dogs were placed on cardiopulmonary bypass. The right and left ventricles were vented, vent flows were measured volumetrically, and intracavitary left ventricular (LV) pressures were monitored. After induction of ischemia by aortic cross-clamping and infusion of cardioplegic solution, six different microspheres 7 to 10 microns in diameter were injected into the aorta at six different times to measure myocardial blood flow during the following interventions:vent drainage of the right or left ventricle or both, proximal ligation of both coronary arteries, severance of the proximal pulmonary artery or the ascending aorta or both, and ligation of the bronchial arteries. Without effective LV venting, LV intracavitary pressure rose to 7.0 +/- 0.1 mm Hg (mean +/- standard error of the mean) and myocardial blood flow in the anterior left ventricle was 2.3 +/- 1.3 ml/100 gm/min. When the LV vent was opened, vent flow was 35.9 +/- 3.5 ml/min and myocardial blood flow fell to 0.3 +/- 0.2 ml/100 gm/min. Right ventricular (RV) vent flow was absent except when the LV vent was occluded, and this RV vent flow was abolished by ligating the coronary arteries. With bronchial artery ligation, LV vent flow ceased and myocardial blood flow was virtually absent. These studies demonstrate that myocardial blood flow does occur during induced ischemia, but that the source of this blood flow is primarily through systemic-pulmonary channels. True noncoronary collateral myocardial blood flow was virtually nonexistent.     

Effect of coronary artery occlusion on myocardial protection by retroperfusion of cardioplegic solutions

Coronary artery stenoses impede delivery of cardioplegic solutions infused through the aortic root. Therefore, the efficacy of retroperfusion of cardioplegic solution through the coronary sinus was assessed in dogs subjected to cold, potassium cardioplegic arrest. Group I (N = 15) had the left anterior descending (LAD) coronary artery occluded throughout ischemia while Group II (N = 15) had a patent LAD. Transmural biopsies of both the left ventricular (LV) apex and right ventricle (RV) were assayed for adenosine triphosphate (ATP) and creatine phosphate (CP). Regional wall temperatures were sequentially monitored. The time from aortic cross-clamping to electrical arrest varied widely, but the mean arrest time of each group was similar (174 +/- 22 vs 175 +/- 28 sec). (table; see text) Comparable depletion of ATP stores (vs preischemia) occurred in each ventricle regardless of coronary artery patency. Similarly, CP stores were depleted 60-72% (P less than 0.01) during ischemia. Mean temperatures during arrest of the RV and LV (17.2-19.5 degrees C) did not differ and were not affected by LAD occlusion. Coronary venous resistance remained constant with repetitive infusions. These data suggest that myocardial protection with coronary sinus retroperfusion is independent of arterial patency, but is suboptimal, perhaps due to the prolonged time needed to induce ventricular arrest.     

Regional coronary hemodynamics during isoflurane-nitrous oxide anesthesia in patients with ischemic heart disease

The effects of 1.5 MAC isoflurane-nitrous oxide anesthesia on central hemodynamics, regional coronary blood flow, myocardial oxygenation, and lactate balance were investigated in 13 patients with coronary artery disease. Mean arterial pressure was reduced 45% mainly because of systemic vasodilation. Great cardiac venous flow (GCVF) decreased, whereas total coronary sinus blood flow (CSF) was unchanged. Total coronary resistance and resistance in the area drained by the GCVF decreased as did myocardial oxygen extraction, demonstrating coronary vasodilation. The GCVF/CSF ratio did not decrease despite the reduction in resistance to left ventricular ejection. Seven patients had ECG and metabolic indications of myocardial ischemia (lactate extraction reduced from 22 +/- 5% to 7 +/- 3%, P less than 0.02 for the group). Changes in GCVF and oxygen consumption in the corresponding area correlated closely (r = 0.943). However, the regression line was shifted to the left and three patients, who became ischemic, had an increase in GCVF despite unchanged or decreased myocardial oxygen demand. It is concluded that isoflurane may cause coronary blood flow redistribution with regional myocardial ischemia in patients with coronary artery disease.     

Effects of midazolam on the coronary circulation in patients with coronary artery disease

The effects of midazolam on coronary sinus blood flow (CSBF), myocardial oxygen consumption (MVO2), and myocardial lactate balance were investigated in eight patients with stable coronary artery disease undergoing cardiac catheterization. Coronary sinus blood flow was measured by continuous thermodilution. Arterial and coronary sinus blood were analyzed for oxygen and lactate content. The determinants of left ventricular (LV) performance were obtained from the cardiac output measured by thermodilution and from left heart catheterization data. All data were obtained before, and 5 and 15 min after midazolam, 0.2 mg X kg-1 iv. Sleep was induced in all patients after administration of midazolam and persisted throughout the entire study period. Mean aortic and LV end-diastolic pressure were decreased from control values (-15 and -44%, respectively), as well as cardiac index and stroke index (-10 and -15%, respectively). Heart rate increased moderately (+8%), while no change in systemic vascular resistance and maximum velocity of shortening (Vmax) were observed. Midazolam administration was followed by a decrease of CSBF (-24%) and of MVO2 (-26%). Coronary vascular resistance did not change, but coronary sinus oxygen tension increased slightly, suggesting a mild alteration in normal autoregulation. However, no evidence of myocardial ischemia occurred, as judged by the absence of changes in the: 1) ECG, 2) myocardial lactate extraction, and 3) relaxation time constant. These results suggest that midazolam may be used safely in patients with coronary artery disease.     

Regional coronary blood flow and coronary vascular reserve in unanesthetized calves at rest and during pharmacologic stress

The present study was carried out: (a) To determine whether the uniformity of transmural left ventricular (LV) myocardial blood flow (MBF) is due to a gradient of vasoactive tone or to a gradient of vascularity favoring the deeper layers. (b) To examine the changes in right ventricular (RV) MBF and coronary vascular reserve of conscious calves brought about by various kinds of stress. Hemodynamics and MBF (15-μm tracer microspheres) were studied in six awake calves before and during maximal coronary vasodilatation induced by adenosine infusion (4 μM/kg/min). Although heart rate increased by 46% and mean aortic blood pressure decreased by 29% with adenosine infusion, the RV and LV MBF had increased by 710 and 394%, respectively. Thus under basal conditions we found RV coronary vascular reserve to be greater than that in the LV. The endo:epi ratio during maximal coronary vasodilatation did not decrease below 1.00 in both ventricles. This suggested that normally higher LV subendocardial perfusion (i.e., endo:epi > 1.0) of resting awake calves is most likely not due to a out → in diminishing gradient of vasomotor tone. Minimal coronary vascular resistance was identical for both ventricles. MBF was also studied in six additional calves at control, during isoproterenol infusion (0.2 μg/kg/min), pacing, and acute volume overload before and after propranolol pretreatment. The percentage increase in RV MBF per unit weight was higher than that in the LV MBF with each stress. With isoproterenol stress, LV endo:epi had decreased significantly below 1.0 while RV endo:epi was well maintained. Propranolol pretreatment significantly blunted the increase in RV and LV MBF brought about by acute volume overload.     

The comparative cardiovascular effects of sevoflurane with halothane and isoflurane

Using closed chest dogs, the cardiovascular effects of sevoflurane were compared with those of halothane and isoflurane in equipotent doses of 1.0, 1.5, 2.0, 2.5 and 3.0 MAC. They were evaluated by the changes of arterial blood pressure, central venous pressure, pulmonary artery pressure, maximum rate of left ventricular pressure rise (LV dp/dt), cardiac output and coronary sinus blood flow. The suppression of left cardiac function by sevoflurane was less than that of halothane, but was greater than that of isoflurane. Heart rate, systemic vascular resistance with sevoflurane were slightly lower than that of isoflurance. The coronary sinus blood flows with sevoflurane and isoflurane were significantly (P < 0.05 at 1.0 MAC, P < 0.005 at 2.0 MAC) higher than halothane. There was no significant difference on coronary sinus flow between sevoflurane and isoflurane. The depth of anesthesia could be quickly changed by adjustment of inspired sevoflurane concentration in comparison with the other two anesthetics.(Kazama T, Ikeda K: The comparative cardiovascular effects of sevoflurane with halothane and isoflurane. J Anesth 2: 63–68, 1988)