Cardiovascular and electrophysiologic interactions between diltiazem and isoflurane in the dog

The effects of the calcium entry blocker diltiazem (iv loading dose 0.4 mg/kg, iv maintenance dose 0.4 mg/min) and subsequent isoflurane-induced hypotension to mean aortic pressures of 70 and 55 mmHg on global and regional right ventricular (RV) and left ventricular (LV) performance (ultrasonic dimension technique), on coronary (electromagnetic flow probes) and systemic hemodynamics, and on electrophysiologic parameters (PR, QRS, QTc intervals) were studied in eight open-chest dogs, anesthetized and paralyzed by continuous infusions of fentanyl and pancuronium. Diltiazem at a plasma concentration of 282 +/- 33 ng/ml (mean +/- SE) caused significant (P less than 0.05) increases in coronary blood flows, and decreases in coronary and systemic vascular resistances with only little effect on global and regional RV and LV function. However, the PR interval increased by 40%, and three animals developed II degrees atrioventricular block type I. At stable diltiazem plasma levels, administration of isoflurane caused dose-dependent decreases in myocardial segment shortening and stroke volume with unchanged LV or increased RV preload, and little changed RV or reduced LV afterload indicating myocardial depression. Coronary and systemic vascular resistances remained unaffected. At the higher concentration of isoflurane (mean inspired 1.3 +/- 0.2%), seven animals developed intermittent sinus node arrests with pauses up to 12 s followed by intermittent junctional escape or sinus rhythms. Similar interactions might develop in patients on diltiazem receiving isoflurane.     

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.     

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.     

Calcium reverses global and regional myocardial dysfunction caused by the combination of verapamil and halothane

In order to evaluate the effects of the combination of halothane and verapamil on left ventricular function and coronary blood flow (CBF), six sheep were anaesthetized with halothane (1.2% inspired) and given increasing cumulative doses of intravenous verapamil. Regional myocardial function was assessed by sonomicrometry in the areas supplied by the left anterior descending coronary artery (LAD) and the left circumflex coronary artery (LC). Changes in global haemodynamics, atrioventricular conduction, LV relaxation and systolic shortening after 0.32 mg X kg-1 intravenous verapamil indicated impaired left ventricular function. Significant myocardial dysfunction (post-systolic shortening) occurred in the LAD territory, accompanied by a 64% decrease (42 +/- 6 to 15 +/- 3, P less than 0.01) in coronary perfusion pressure (CPP). Coronary blood flow in the LC segment decreased 83% (102 +/- 15 to 17 +/- 13, P less than 0.01) as coronary reserve was exhausted with the decrease in CPP. Calcium chloride reversed the impairment of global and regional myocardial function observed with verapamil, improved the impaired left ventricular relaxation, but did not significantly alter atrioventricular conduction. Thus the combination halothane-verapamil can cause significant left ventricular depression and myocardial dysfunction, possibly by inducing subendocardial ischaemia or by direct pharmacologic effect. Calcium chloride reverses this regional myocardial dysfunction as well as the deleterious global haemodynamic changes caused by halothane-verapamil; however, the changes in atrioventricular conduction are not corrected by calcium.     

Studies of retrograde cardioplegia. II. Advantages of antegrade/retrograde cardioplegia to optimize distribution in jeopardized myocardium

This study tests the hypothesis that retrograde/antegrade cardioplegic delivery can overcome the limitations of poor cardioplegic distribution resulting from either technique alone and, potentially, may expand the safety of using internal mammary artery grafts in cardiac muscle in jeopardy of inadequate cardioplegic protection. Jeopardized myocardium was produced in 20 dogs by ligating the left anterior descending coronary artery for 15 minutes before starting cardiopulmonary bypass and by 1 hour of aortic clamping with multidose 6 degrees C cold blood cardioplegia. Five dogs received antegrade cardioplegia via the aortic root. Ten dogs received retrograde cardioplegia via the coronary sinus. Five additional dogs received retrograde/antegrade cardioplegia via both routes. The ligature on the left anterior descending coronary artery was removed after aortic unclamping, and regional myocardial temperature (thermistor probe), segmental shortening (ultrasonic crystals), and global left ventricular and right ventricular myocardial function were evaluated. Antegrade cardioplegia produced excellent right ventricular cooling (14 degrees C) and allowed complete right ventricular functional recovery. However, it failed to cool muscle supplied by the left anterior descending coronary artery (only 31 degrees versus 12 degrees C, p less than 0.05), postischemic global left ventricular function recovered only 38% (p less than 0.05), and segmental shortening in the region supplied by the left anterior descending coronary artery recovered only 22% (p less than 0.05). Retrograde cardioplegia produced homogeneous cooling (17 degrees C) and allowed near normal recovery of global and regional left ventricular function (99% and 86%), but right ventricular cooling was variable (19 degrees to 30 degrees C) and right ventricular function recovered inconstantly (range 64% to 100%, average 82%). The best myocardial protection occurred after retrograde/antegrade cardioplegia; myocardial cooling was homogeneous, left ventricular and right ventricular global function recovered completely (95% and 90%), and regional contractility in muscle supplied by the left anterior descending coronary artery returned to 84% of control. We conclude that retrograde/antegrade cardioplegia provides better myocardial protection than either technique alone, ensures good cardioplegic distribution to the left and right ventricles, and allows regional delivery of cardioplegic flow to segments supplied by occluded arteries.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of deliberate hypotension on the ischemic heart during isoflurane anesthesia--a comparison of prostaglandin E1 and sodium nitroprusside]

The effects of hypotension induced by prostaglandin E1 (PGE1) or sodium nitroprusside (SNP) on regional myocardial function and metabolism were studied in a canine heart with coronary artery stenosis. Ultrasonic dimension technique was used to assess left ventricular performance. Fourteen open-chest mongrel dogs were anesthetized with isoflurane and mean aortic pressure was maintained at approximately 80 mmHg. The left circumflex coronary artery blood flow was reduced by 40% using a screw flow regulator without affecting global and regional myocardial function. The severity of stenosis was considered almost critical. PGE1 (n = 7) or SNP (n = 7) was administered to reduce mean aortic pressure to 50 mmHg. There were no significant differences between PGE1 and SNP regarding their effect on systemic hemodynamics. Nevertheless SNP decreased percent segment shortening in the stenosed area from the pre-hypotension value more significantly than PGE1 (55.0 +/- 10.8% versus 24.2 +/- 7.3%). This suggests that regional myocardial ischemia is more deteriorated during SNP-induced hypotension. It seems that PGE1-induced hypotension is safer when it is applied to patients with coronary artery disease.     

Regional blood flow and tissue oxygen pressures of the collateral-dependent myocardium during isoflurane anesthesia in dogs

The authors investigated the effects of isoflurane on blood flow and tissue oxygen pressures of a collateral-dependent myocardium. Seventeen dogs divided into two groups were studied 3-4 weeks after implantation of ameroid coronary artery constrictors to completely occlude the proximal part of the left anterior descending artery. Experiments were performed during anesthesia with an opiate that was infused intravenously throughout the experiments. In Group 1 (n = 9), measurements were obtained during control and during isoflurane- (1.6-2.2 vol%) induced hypotension (mean arterial pressure, 60 mmHg). In Group 2 (n = 8), the identical protocol was applied, but norepinephrine was infused to maintain normotension. Dipyridamole effects were studied in five animals of Group 2 after a second control period at least 1 h after discontinuation of isoflurane. Isoflurane-induced hypotension caused reductions of blood flow and surface tissue oxygen pressures in the collateral flow-dependent area. Vasodilation in the normal left ventricular areas was demonstrated by an unchanged blood flow despite a reduced oxygen consumption and by a significantly increased coronary sinus hemoglobin oxygen saturation. When arterial pressure was maintained at its control level by norepinephrine, tissue oxygen pressures remained constant and collateral as well as normal area flow increased significantly during isoflurane. Coronary vascular resistance was lower during administration of isoflurane and norepinephrine compared with that during isoflurane induced hypotension, suggesting a significant contribution of tissue oxygen demand in regulation of coronary vascular resistance. At comparable levels of arterial pressure and left ventricular oxygen consumption, normal zone blood flow was significantly higher during dipyridamole than during isoflurane and norepinephrine. Thus, isoflurane-induced hypotension decreased blood flow and tissue oxygen pressures of collateral flow-dependent myocardial areas. However, neither isoflurane nor dipyridamole caused such alterations when arterial pressure was normal.     

Isoflurane-enhanced recovery of canine stunned myocardium: role for protein kinase C?

BACKGROUND: Isoflurane enhances the functional recovery of postischemic, reperfused myocardium by activating adenosine A1 receptors and adenosine triphosphate-regulated potassium channels. Whether protein kinase C is involved in this process is unknown. The authors tested the hypothesis that inhibition of protein kinase C, using the selective antagonist bisindolylmaleimide, attenuates isoflurane-enhanced recovery of stunned myocardium in dogs. METHODS: Fifty dogs were randomly assigned to receive intracoronary vehicle or bisindolylmaleimide (2 or 8 microg/min) in the presence or absence of isoflurane (1 minimum alveolar concentration). Five brief (5 min) coronary artery occlusions interspersed with 5-min reperfusion periods followed by 180 min of final reperfusion were used to produce myocardial stunning. Hemodynamics, regional segment shortening, and myocardial blood flow (radioactive microspheres) were measured at selected intervals. RESULTS: There were no differences in baseline hemodynamics, segment shortening, or coronary collateral blood flow between groups. Isoflurane significantly (P<0.05) decreased heart rate, mean arterial pressure, rate pressure product, and the maximum rate of increase of left ventricular pressure (+dP/dt(max)) in the presence or absence of bisindolylmaleimide. Sustained contractile dysfunction was observed in dogs that received vehicle (recovery of segment shortening to 12+/-8% of baseline), in contrast to those that received isoflurane (75+/-7% recovery). Bisindolylmaleimide at a dose of 2 microg/min alone enhanced recovery of segment shortening (50+/-7% of baseline) compared with vehicle-pretreated dogs, and isoflurane in the presence of 2 microg/min bisindolylmaleimide further enhanced recovery of contractile function (79+/-8% of baseline). In contrast, 8 microg/min bisindolylmaleimide alone (32+/-12%) or combined with isoflurane (37+/-17%) did not enhance recovery of segment shortening compared with vehicle-pretreated dogs. CONCLUSIONS: The results indicate that protein kinase C inhibition using low doses of bisindolylmaleimide alone produces cardioprotection, and isoflurane further enhances this protection. In contrast, high doses of bisindolylmaleimide are not cardioprotective in the presence or absence of isoflurane. A role for protein kinase C during isoflurane-induced recovery of the stunned myocardium cannot be excluded.     

Mechanism of Myocardial Protection by Isoflurane: Role of Adenosine Triphosphate-regulated Potassium (K sub ATP) Channels

Background: The mechanism of the protective actions of volatile anesthetics in ischemic myocardium has not been clearly elucidated. The role of myocardial adenosine triphosphate-regulated potassium (KATP) channels in isoflurane-induced enhancement of recovery of regional contractile function after multiple brief occlusions and reperfusion of the left anterior descending coronary artery (LAD) was studied in dogs anesthetized with barbiturates.

Methods: Dogs (n = 32) were instrumented to measure left ventricular and aortic blood pressure, cardiac output, LAD coronary blood flow velocity, and subendocardial segment length. Regional myocardial perfusion was measured using radioactive microspheres. Hemodynamics and percentage segment shortening (%SS) in the LAD perfusion territory were evaluated after instrumentation was complete; after pretreatment with the KATP channel antagonist, glyburide (0.05 mg/kg sup -1) or drug vehicle (polyethylene glycol in ethyl alcohol; control experiments); and in the presence or absence of 1 MAC isoflurane administered for 30 min before and during five 5-min occlusions and reperfusion of the LAD in four experimental groups. Isoflurane was discontinued at the onset of the final reperfusion period. Measurements of hemodynamics, %SS, and myocardial perfusion were repeated at several intervals during 180 min after reperfusion of the LAD.

Results: Left anterior descending coronary artery occlusion caused regional dyskinesia during each 5-min occlusion in each dog. Control and glyburide-pretreated dogs demonstrated poor recovery of %SS by 180 min after reperfusion (2 +/- 10 and 7 +/- 6% of baseline, respectively). In contrast, dogs anesthetized with isoflurane exhibited complete recovery of function (%SS) by 180 min after reperfusion (82 +/- 8% of baseline). Enhanced recovery of regional contractile function by isoflurane was abolished by pretreatment with glyburide 180 min after reperfusion (16 +/- 10% of baseline). Improvement of functional recovery of stunned myocardium by isoflurane, and the blockade of this action by glyburide, was not associated with changes in hemodynamics or regional myocardial perfusion.     

Isoflurane causes more severe regional myocardial dysfunction than halothane in dogs with a critical coronary artery stenosis

The effects of 1) isoflurane (ISO)- and halothane (HAL)-induced hypotension to a mean aortic pressure (AoP) of 55 mmHg, and 2) of substituting ISO and HAL for each other at a mean AoP of 55 mmHg on global and regional left ventricular performance (ultrasonic dimension technique) and on coronary hemodynamics (electromagnetic flow probes) were studied in eight open-chest dogs (anesthetized and paralyzed by continuous infusions of fentanyl and pancuronium) with a critical coronary artery stenosis (micrometer-controlled snare) of the left anterior descending coronary artery (LAD). The stenosis reduced resting coronary blood flow by 5% (P less than 0.05) without affecting global or regional myocardial performance. HAL- and ISO-induced hypotension caused comparable decreases in global cardiac function, but regional myocardial dysfunction in the area of stenosis and the reduction in coronary flow through the stenosed LAD were more pronounced during ISO. Substitution of HAL for ISO at constant mean AoP, heart rate, end-diastolic dimensions and pressures, and stroke volume resulted in significant (P less than or equal to 0.05) amelioration of regional myocardial dysfunction (improvement in contraction amplitude, disappearance of paradoxical systolic lengthening and akinesis), a 20% increase in flow through the stenosed LAD, and a 20% decrease in flow through the unobstructed left circumflex coronary artery. These data suggest that, in the presence of a critical coronary artery stenosis: 1) ISO- and HAL-associated hypotension result in comparable decreases in global cardiac function, 2) ISO-associated hypotension is more likely to cause severe regional myocardial dysfunction suggestive of ischemia than equal degrees of HAL-associated hypotension, and 3) the different effects of HAL and ISO on ischemic myocardial segments at equally reduced coronary perfusion pressure are primarily related to their different effects on coronary vasomotor tone.     

Isoflurane-enhanced Recovery of Canine Stunned Myocardium: Role for Protein Kinase C?

Background: Isoflurane enhances the functional recovery of postischemic, reperfused myocardium by activating adenosine A1 receptors and adenosine triphosphate-regulated potassium channels. Whether protein kinase C is involved in this process is unknown. The authors tested the hypothesis that inhibition of protein kinase C, using the selective antagonist bisindolylmaleimide, attenuates isoflurane-enhanced recovery of stunned myocardium in dogs.

Methods: Fifty dogs were randomly assigned to receive intracoronary vehicle or bisindolylmaleimide (2 or 8 [mu]g/min) in the presence or absence of isoflurane (1 minimum alveolar concentration). Five brief (5 min) coronary artery occlusions interspersed with 5-min reperfusion periods followed by 180 min of final reperfusion were used to produce myocardial stunning. Hemodynamics, regional segment shortening, and myocardial blood flow (radioactive microspheres) were measured at selected intervals.

Results: There were no differences in baseline hemodynamics, segment shortening, or coronary collateral blood flow between groups. Isoflurane significantly (P < 0.05) decreased heart rate, mean arterial pressure, rate pressure product, and the maximum rate of increase of left ventricular pressure (+dP/dtmax) in the presence or absence of bisindolylmaleimide. Sustained contractile dysfunction was observed in dogs that received vehicle (recovery of segment shortening to 12 +/- 8% of baseline), in contrast to those that received isoflurane (75 +/- 7% recovery). Bisindolylmaleimide at a dose of 2 [mu]g/min alone enhanced recovery of segment shortening (50 +/- 7% of baseline) compared with vehicle-pretreated dogs, and isoflurane in the presence of 2 [mu]g/min bisindolylmaleimide further enhanced recovery of contractile function (79 +/- 8% of baseline). In contrast, 8 [mu]g/min bisindolylmaleimide alone (32 +/- 12%) or combined with isoflurane (37 +/- 17%) did not enhance recovery of segment shortening compared with vehicle-pretreated dogs.     

Adverse effects of halothane in a canine model of acute right ventricular hypertension

The effects of acute right ventricular (RV) hypertension (RVH) induced by pulmonary artery (PA) constriction, and of two concentrations (mean inspired 0.8 and 1.5%) of halothane (HAL) during RVH on global and regional RV performance (ultrasonic dimension technique), and on coronary hemodynamics (electromagnetic flow probes) were studied in 12 open-chest dogs anesthetized and paralyzed by continuous infusions of fentanyl and pancuronium. Following PA constriction, RV systolic pressure more than doubled, RV end-diastolic and systolic dimensions increased, and stroke volume (SV) and segment shortening fell (P all less than 0.05). There was no evidence of regional myocardial dysfunction (i.e., akinesis, systolic lengthening, postsystolic shortening), and reactive hyperemia in response to right coronary artery occlusion was present. Subsequent addition of HAL (0.8%) resulted in further increases in end-diastolic and systolic dimensions, and in marked decreases in right coronary blood flow, segment shortening, SV, and aortic pressure. During HAL 1.5% (range: 1.2-1.6%), regional myocardial dysfunction developed in three animals, reactive hyperemia was abolished in five out of six animals tested, and metabolic acidosis developed. Release of PA constriction during 1.5% HAL in seven animals resulted in improved global and regional RV performance, disappearance of regional myocardial dysfunction, and restoration of reactive hyperemia. In this canine model of acute RVH, increasing concentrations of HAL led to increasing deterioration in global and regional RV performance most likely due to inadequate coronary perfusion.     

Effects of isoflurane and fentanyl on ischemic myocardium in dogs: assessment by end-systolic measurements

The effect of anesthetics on ischemic myocardium to which blood was supplied by a stenotic coronary artery was investigated in dogs. The ischemia was assessed by regional wall motion (ultrasonic dimension technique) using fractional shortening (FS) [(EDL - ESL)/EDL x 100] and end-systolic pressure-segment length relationships (ESPLR). The latter is considered to be a more load-independent measure of regional myocardial function. Isoflurane and fentanyl were chosen as anesthetics of current interest. On reducing the left circumflex coronary artery (LCX) flow to approximately 50% of its resting value, a decrease in FS and a rightward shift in ESPLR were observed in myocardium perfused by the LCX. Simultaneously, increases in FS were observed in the nonischemic area perfused by the left anterior descending coronary artery (LAD), which was most likely due to the intraventricular unloading effect. No significant changes of ESPLR were observed in the area supplied by LAD. Isoflurane induced a dose-dependent decrease in FS and a rightward shift in ESPLR in the ischemic myocardial segment, whereas fentanyl caused an increase in FS and tended to shift ESPLR leftward in the same area. The results suggest that isoflurane may have deleterious effects on preexisting myocardial ischemia, whereas fentanyl may not when loading conditions are taken into consideration. Fractional shortening and ESPLR seem to provide similar information about regional myocardial function.     

Postsystolic shortening of canine left ventricle supplied by a stenotic coronary artery when nitrous oxide is added in the presence of narcotics

The effects of fentanyl and sufentanil with and without N2O on left ventricular myocardium supplied by a critically narrowed and a normal coronary artery were studied in 16 dogs. Regional ventricular function was measured by recording ventricular segment length with the use of ultrasonic length detectors in the left anterior descending (LAD) and the left circumflex (LC) coronary artery territories before and during critical stenosis of the LAD. Critical stenosis was documented by the absence of a hyperemic response following a 10-s total occlusion of the LAD. Hemodynamic variables (aortic flow and pressure, left ventricular pressure, heart rate, and coronary blood flow) were measured and the first derivative of left ventricular pressure (LVdP/dt) and coronary perfusion pressure derived. Eight dogs received fentanyl 100 micrograms X kg-1 followed by an infusion of 1 microgram X kg-1 X min-1 while ventilated with O2:N2 (1:2), and eight dogs received sufentanil 30 micrograms X kg-1 with an infusion of 0.3 micrograms X kg-1 X min-1. Replacement of N2 with N2O produced evidence of mild systolic myocardial depression but no dysfunction in either group. After application of the critical constriction, the addition of N2O rapidly produced evidence of dysfunction with significant postsystolic shortening only in the LAD territory. This was not accompanied by hypotension or a decrease in coronary flow and was not always reversible. Higher infusion rates of either narcotic (fentanyl 2 micrograms X kg-1 X min-1, 4 micrograms X kg-1 X min-1; sufentanil 0.6 micrograms X kg-1 X min-1, 1.2 micrograms X kg-1 X min-1) in the absence of N2O did not produce dysfunction but had no protective effect when N2O was added.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preserved myocardial blood flow and oxygen supply-demand balance with active coronary perfusion during simulated off-pump coronary artery bypass grafting.

BACKGROUND: During off-pump coronary artery bypass surgery, concern remains about the possible myocardial injury associated with the transient occlusion and stabilization of the target vessels. Although intraluminal shunts are used to avoid ischemia during graft anastomosis, blood flow through the shunts can be affected by upstream pressure and inherent resistance, resulting in reduced blood flow during hypotension or severe proximal stenosis. METHODS: In anesthetized dogs regional myocardial blood flow (microspheres), oxygen consumption, lactate extraction, and systolic shortening (sonomicrometry) were measured in the myocardium served by the left anterior descending coronary artery with native perfusion after interposition of a 2.25-mm shunt (> or = 90% of left anterior descending diameter) and during active coronary perfusion with a constant flow pump. Measurements were made under normotension and hypotension produced by partial caval occlusion to reduce arterial pressure by 50%. RESULTS: Interposition of the shunt reduced blood flow by 67.8%, regional oxygen delivery by 59.8%, and systolic shortening by 45.6% relative to baseline, but lactate extraction (31.0% vs 31.2%) and oxygen supply-consumption (O(2)S/myocardial oxygen consumption ratio, 2.7 +/- 0.5 vs 2.6 +/- 0.5) were comparable with baseline values. Hypotension further decreased these physiologic values and was associated with local lactate production (-67.4% extraction) and decreased O(2)S/myocardial oxygen consumption ratio (1.3 +/- 0.1). Active coronary perfusion was associated with regional blood flow, oxygen delivery, systolic shortening, and lactate extraction comparable with baseline values. In contrast to the shunt, active perfusion maintained myocardial flow, oxygen delivery, and lactate extraction during hypotension and normalized the O(2)S/myocardial oxygen consumption ratio, although systolic shortening decreased as a result of ventricular unloading. CONCLUSION: Intraluminal shunts may impede oxygen delivery to the target myocardium, which precipitates regional ischemia during transient hypotension. Active coronary perfusion provides adequate oxygen supply independent of systemic blood pressure.     

Myocardial ischemia in a canine model of pulmonary hypertension and right coronary artery stenosis

This study was performed to study the effects of acute pulmonary embolization (injection of autologous muscle) on global and regional (ultrasonic dimension technique) right ventricular (RV) performance, coronary hemodynamics (electromagnetic flow probes), and gas exchange during underlying critical stenosis (cuff occluder) of the right coronary artery (RCA) in eight open-chest dogs. Resting coronary blood flow (CBF) and regional myocardial performance remained unaffected by the induction of RCA stenosis. Following embolization pulmonary artery (PA) pressure, pulmonary vascular resistance, end-diastolic dimensions and pressure increased, and PA flow, stroke volume (SV), and aortic pressure (AoP) decreased (P less than 0.05). There was a marked decline (60%) in CBF accompanied by severe myocardial dysfunction suggestive of ischemia (akinesis, systolic lengthening, postsystolic shortening) in the area supplied by the stenosed RCA. Gas exchange, lung compliance, and pH worsened. Release of the RCA constriction led to a fourfold increase in CBF, return of PA flow, SV, and AoP to baseline values, and disappearance of regional myocardial dysfunction despite continued pulmonary hypertension. These data indicate that RV function may deteriorate in response to even small increases in afterload if coronary vascular reserve is absent and aortic pressure is allowed to decrease.     

Regional and global myocardial function in the dog when nitrous oxide is added to halothane in the presence of critical coronary artery constriction

The effect of substituting 66% nitrous oxide for nitrogen on global and regional myocardial function before and after critical constriction of the left anterior descending coronary artery (LAD) was studied in six open-chested dogs anesthetized with 1% halothane (inspired). Regional myocardial function was measured in the region of the LAD and in the region of the left circumflex artery using sonomicrometry, and LAD blood flow was measured. Administration of nitrous oxide produced moderate depression of global performance. Regional shortening in both myocardial segments was reduced, and dysfunction also appeared in the LAD segment. This dysfunction was observed in the presence of both normal coronary blood flow, and after critical constriction. The appearance of dysfunction when coronary blood flow was unimpaired suggests that ischemia may not be the only cause of regional myocardial dysfunction.     

Phenylephrine does not limit myocardial blood flow or oxygen delivery during isoflurane-induced hypotension in dogs.

Experiments were performed on seven fentanyl-pentobarbital-anesthetized, open-chest dogs to determine whether stimulation of coronary alpha 1-adrenergic receptors by phenylephrine causes coronary vasoconstriction and impaired myocardial oxygen delivery when phenylephrine is infused to correct isoflurane-induced hypotension. Myocardial blood flow was measured with radioactive microspheres, and myocardial oxygen and lactate extraction were determined. The Fick equation was used to calculate myocardial oxygen consumption. Measurements were obtained (a) under control conditions, (b) after a 30-min inhalation of isoflurane sufficient to decrease mean aortic pressure by 30%, and (c) while maintaining administration of isoflurane, 5-10 min after restoration of mean aortic pressure by intravenous infusion of phenylephrine. Isoflurane-induced hypotension was accompanied by a baroreceptor-mediated increase in heart rate and by a decrease in myocardial oxygen consumption; however, myocardial blood flow was maintained, resulting in decreased oxygen extraction and increased coronary sinus PO2, thus implying a direct coronary vasodilating effect for isoflurane. Lactate extraction was unaffected. Phenylephrine infusion during inhalation of isoflurane returned mean aortic pressure and heart rate to their respective control values, and it did not change myocardial oxygen consumption, myocardial blood flow, myocardial oxygen extraction, coronary sinus PO2, or lactate extraction from values obtained during isoflurane alone. These latter findings are consistent with undiminished coronary vasodilation by isoflurane in the presence of phenylephrine. In conclusion, infused phenylephrine to restore aortic pressure during isoflurane administration had no vasoconstrictor effect in the coronary circulation and did not impair myocardial oxygen delivery. Apparently, the direct coronary vasodilating action of isoflurane completely nullified phenylephrine-induced vasoconstriction via local alpha 1-adrenergic receptors.     

Acute colloid administration increases ischemia in the myocardium supplied by a stenotic coronary artery.

The effect of acute colloid administration was evaluated in the pig heart in which an external coronary artery stenosis was applied. Seven pigs received thiopentone and halothane anesthesia. Ultrasonic crystals were inserted in the myocardium supplied by the left anterior descending (LAD) and circumflex coronary arteries. Left ventricular pressure was measured and regional myocardial function was quantified with the pressure-length loop and the end-systolic pressure-length ratio. A significant stenosis was applied to the LAD artery, after which the animal received fixed colloids to increase the left ventricular end-diastolic pressure. Regional myocardial ischemia was defined with reference to postsystolic shortening and lactate production from the region supplied by the LAD artery. The application of the stenosis caused an increase in postsystolic shortening from 9.62% +/- 4.24% to 26.12% +/- 5.81% (mean +/- SEM; P less than 0.05), and lactate extraction changed from 15.88% +/- 2.38% to -9.56% +/- 5.32% (P less than 0.05). Acute colloid administration increased the left ventricular end-diastolic pressure from 9.71 +/- 1.77 to 15.93 +/- 2.07 mm Hg (P less than 0.05), and lactate extraction further decreased to -76.63% +/- 19.19% (P less than 0.05). Postsystolic shortening increased to 36.22% +/- 5.10% (P less than 0.05). The oxygen tension in the venous blood draining the LAD region decreased from 36.74 +/- 9.37 to 17.34 +/- 1.23 mm Hg (P less than 0.05). We conclude that in the acute pig model, augmentation of the preload worsens regional myocardial ischemia in an area supplied by a stenotic coronary artery.     

Comparative effects of halothane, enflurane, and isoflurane at equihypotensive doses on cardiac performance and coronary and renal blood flows in chronically instrumented dogs.

In order to compare equihypotensive effects of the three available volatile anesthetics, halothane, enflurane, and isoflurane, dogs were chronically instrumented for measurement of: arterial, left ventricular, and left atrial blood pressures; rate of rise of left ventricular blood pressure; myocardial wall thickening (pulsed Doppler); cardiac output (pulmonary artery electromagnetic flow meter); and coronary and renal blood flows (pulsed Doppler flow meters). All three anesthetics were administered on different days in random order to each dog (n = 10) at doses necessary to decrease mean arterial pressure to 70 and 45 mmHg and two intermediate arterial blood pressures. Changes in cardiac function and regional blood flows were compared to the awake resting state and between anesthetics using analysis of variance and paired t tests. All three anesthetics produced increases in heart rate and decreases in left ventricular dP/dt, myocardial thickening fraction, and stroke volume with the hypotension. The decreases in cardiac performance were similar among the anesthetics except at the high dose (mean arterial pressure = 45 mmHg). During this profound hypotension, cardiac performance was better maintained during isoflurane anesthesia and most depressed by enflurane anesthesia. Coronary and renal blood flows were well preserved with all three anesthetics even at mean arterial pressures of 45 mmHg. Our results suggest that isoflurane may be more beneficial than halothane or enflurane for producing profound intentional hypotension (less than 50 mmHg mean arterial pressure), although extrapolation from animal experiments to the clinical situation should be used with caution.