W. A. Ryder

A comparison of the effects of fentanyl and propofol on left ventricular contractility during myocardial stunning

Background: The intravenous anaesthetic propofol has been shown to possess free radical scavenging activity and calcium channel blocking effects in a number of in vitro models. We decided to compare the effects of propofol with those of fentanyl on myocardial contractility during and after ischaemia to determine whether propofol could protect the heart and improve recovery of ventricular contractile function in open‐chested dogs.

Effects of Halothane on Left Ventricular Relaxation and Early Diastolic Coronary Blood Flow in the Dog

The effects of graded concentrations of halothane on left ventricular relaxation and phasic coronary blood flow (CBF) were studied in six open-chest, anesthetized dogs. Global and regional left ventricular function were measured. Besides the expected dose-dependent depression of contractility, regional shortening, and cardiac output, halothane caused significant increases in the time constant of relaxation (Trelax), and decreased and delayed the nadir of peak negative left ventricular dP/dt. Dose-dependent reductions of CBF were noted. Percentage CBF during isovolumic relaxation was significantly reduced and showed a strong inverse correlation with Trelax. Halothane appears to interfere with the inactivation process of the heart; this in turn may impede the early rise in CBF during isovolumic relaxation.

Graded myocardial ischemia is associated with a decrease in diastolic distensibility of the remote nonischemic myocardium in the anesthetized dog

OBJECTIVES This study was designed to investigate the changes in regional distensibility of the ischemic segment and of a remote nonischemic segment brought about by graded myocardial ischemia. BACKGROUND Ventricular distensibility is a major determinant of left ventricular end-diastolic pressure. The effects of graded myocardial ischemia on the regional distensibility of the ischemic area have not been studied. Moreover, there are few data on the effects of myocardial ischemia on the regional distensibility of the nonischemic myocardium. METHODS Nine anesthetized open chest mongrel dogs were fitted with instruments to measure left ventricular pressure and circumferential length (sonomicrometry) in the ischemic segment and in a nonischemic segment. The pressure-length relation was modified by stepwise infusion and withdrawal of 200 ml of each dogs own blood over 30 min in five consecutive stages of regional ischemia. Unstressed dimensions were obtained by repeated inferior vena cava occlusions. In both segments, regional distensibility was assessed at end-diastole by means of the constants of the pressure-length (chamber stiffness), the pressure-strain and the force-strain (myocardial stiffness) relations. RESULTS In the ischemic segment, partial and complete coronary occlusions were associated with a twofold increase in the chamber stiffness constant, the pressure-strain constant and the myocardial stiffness constant, whereas in the nonischemic segment the chamber stiffness constant, the pressure-strain constant and the myocardial stiffness constant increased by 50%. CONCLUSIONS Regional myocardial ischemia is associated with a decrease in distensibility of both the ischemic and the remote nonischemic myocardium.

Gradual or abrupt nitrous oxide administration in a canine model of critical coronary stenosis induces regional myocardial dysfunction that is worsened by halothane.

The existence of a dose-response relation between nitrous oxide concentration and regional dysfunction in compromised myocardium, and whether or not halothane-induced myocardial depression alleviated this regional dysfunction was examined. Nitrous oxide was administered to eight dogs with experimentally induced left anterior descending coronary artery (LAD) critical stenosis during fentanyl (100 micrograms/kg bolus plus 1.5 micrograms.kg-1.min-1) anesthesia. Two modes of nitrous oxide administration were employed: gradual (in steps of 20% inspired, i.e., 0%, 20%, 40%, and 60% inspired) and abrupt (0-60% inspired). Regional myocardial function was assessed by sonomicrometry. Regional dysfunction in the compromised myocardium, in the form of postsystolic shortening (PSS), increased above baseline levels during 40% (4.2 +/- 2.3% to 12.1 +/- 3.9%, P less than 0.05) and 60% (4.2 +/- 2.3% to 12.5 +/- 3.6%, P less than 0.05) inspired nitrous oxide (gradual administration) and also during abrupt 60% nitrous oxide administration (6.4 +/- 2.6% to 9.9 +/- 3.2%, P less than 0.05). After abrupt 60% inspired nitrous oxide administration, halothane (0.7% inspired) was introduced and caused decreases in mean arterial pressure (106.1 +/- 4.5 mm Hg to 76.2 +/- 5.5 mm Hg, P less than 0.05) and peak LV dP/dt (1700 +/- 150 mm Hg/sec to 1100 +/- 100 mm Hg/sec, P less than 0.05). Halothane caused a marked increase in PSS (9.9 +/- 3.2% to 30.8 +/- 12.6%, P less than 0.05). Thus nitrous oxide administration caused regional dysfunction in myocardium supplied by a critically narrowed LAD whether administered gradually or abruptly and at concentrations as low as 40% inspired.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects and interactions of nitrous oxide, myocardial ischemia, and reperfusion on left ventricular diastolic function

The effects of nitrous oxide on left ventricular diastolic function and its potential interactions with ischemia-induced diastolic dysfunction have not been described. Accordingly, we investigated the effects of nitrous oxide in ischemic and remote nonischemic myocardium during baseline, 90 min severe low-flow myocardial ischemia (systolic bulge), and reperfusion in 11 open-chest dogs. Anesthesia was maintained with fentanyl infusion (2 micro g [center dot] kg-1 [center dot] min-1), animals were ventilated with 60% nitrogen in oxygen, and hemodynamic variables were recorded prior to and after the replacement of nitrogen by 60% nitrous oxide. During baseline, nitrous oxide moderately increased chamber stiffness (+10%), myocardial stiffness (+33%), and unstressed length (+4%) and decreased the peak lengthening rate (-10%). Moreover, nitrous oxide decreased regional contractility during baseline (-12% at apex, -8% at base) as well as in nonischemic myocardium during myocardial ischemia (-9%) and reperfusion (-8%). However, nitrous oxide did not modify ischemia-induced systolic or diastolic dysfunction in ischemic myocardium during ischemia and reperfusion. Myocardial ischemia (+45%) and reperfusion (+57%) were associated with an increase in myocardial stiffness of nonischemic myocardium regardless of the anesthetic technique used. This study is the first to demonstrate that in addition to its well established negative inotropic effect, nitrous oxide affects regional diastolic function. (Anesth Analg 1997;84:39-45)

Regional distensibility, chamber stiffness, and elastic stiffness constant in halothane and propofol anesthesia

Nine mongrel dogs were acutely instrumented in order to investigate cardiac stiffness at end-diastole while left ventricular circumferential lengths were measured at two different sites (near-apical region and near-basal region). Two hundred mL of autologous blood were infused and then withdrawn to create different volume loading conditions. Four different anesthetic settings were tested: two concentrations (0.7% and 1.7%) of halothane, and two infusion rates (0.2 mg/min/kg, and 0.4 mg/min/kg) of propofol. Three parameters of cardiac stiffness were calculated: distensibility, chamber stiffness (Kp), and elastic stiffness constant (k). Chamber stiffness and elastic stiffness constant were smaller in the apical region than the basal region under halothane anesthesia at both the 0.7% and 1.7% concentrations. There were no regional differences in elastic stiffness constant (k) under propofol anesthesia at either infusion rate. However, Kp was smaller in the apical region at the low propofol infusion rate. There were no significant differences in Kp and k between the anesthetic agents, or with the increase in concentration of either agent. However, when both agent and concentration were taken into consideration, an increase in stiffness was observed with deepening halothane, but not propofol anesthesia. These results show that assessment of diastolic function must take into consideration both regional differences and the anesthetic agent, because the latter may alter such differences and, thus, alter diastolic function.

Caval occlusion alters the shape of the ischemic and nonischemic pressure-length loop

OBJECTIVES The effects of changes in preload on paradoxical myocardial wall motion during ischemia have been previously studied. However, the studies have been performed using slow volume changes. It was decided to study the effects of fast changes in preload, which would occur during caval occlusion, on the regional pressure-length loops during ischemia. DESIGN Retrospective trial. SETTING Experimental animal laboratory in a university medical center. PARTICIPANTS Ten anesthetized adult dogs. INTERVENTIONS In an open chest preparation, regional ischemia was achieved by occluding the left anterior descending coronary artery for 10 minutes, with sudden caval occlusions being performed to assess the influence of preload on wall motion. MEASUREMENTS AND MAIN RESULTS Left ventricular pressure and regional segmental lengths were measured. During caval occlusion, beat by beat, percent postsystolic shortening and percent systolic bulging in the ischemic region, percent isovolumetric shortening in the nonischemic region, and percent systolic shortening in both regions were calculated. Caval occlusion significantly decreased the end-diastolic pressure (12.62 +/- 1.02 to 3.39 +/- 0.59 mmHg) and length. In the ischemic area, although systolic shortening became more negative (-1.8 +/- 0.79% to -9.65 +/- 1.08%), postsystolic shortening (9.66 +/- 0.73% to 15.53 +/- 1.2%) and systolic bulging (4.6 +/- 0.49% to 12.67 +/- 1.04%) increased. In the nonischemic area, systolic shortening decreased slightly but significantly (18.01 +/- 3.24% to 14.93 +/- 3.64%) as isovolumetric shortening increased (2.77 +/- 0.68 to 7.37 +/- 1.29%). Caval occlusion increased the rightward shift and accentuated the distortion of the ischemic loop. The nonischemic loop displayed a leftward shift of the systolic isovolumetric component and a slight decrease in percent total length change. CONCLUSION Caval occlusion modifies the shape of the pressure-length loop of the ischemic myocardium. This change in shape may interfere with the assessment of regional systolic indexes obtained by caval occlusion in ischemic hearts.

CANINE END-SYSTOLIC PRESSURE-LENGTH RELATIONSHIPS: DEPRESSED BY DILTIAZEM, INVALIDATED BY ISCHAEMIA.

This study was designed to determine whether the end-systolic pressure-length relationship (ESPLR) reflects changes in regional contractility during the imposition of graded ischemia, and whether it is modified by diltiazem during propofol anesthesia. Seven beagles were anesthetized and instrumented to measure left ventricular pressure and subendocardial segment lengths (sonomicrometry) in the region of the left anterior descending (LAD) and circumflex (LC) arteries. Afterload was increased by the tightening of a snare around the descending thoracic aorta. Pressure-length loops were constructed and the slope of the ESPLR and the x-axis intercept, Lo, were calculated. Graded ischemia of the apical myocardium only was accomplished by the tightening of a micrometer-controlled snare around the LAD to produce Critical Constriction (CC), Ischemia 1 and 2 (I1, I2), and Total Occlusion (TO). In the basal LC region, LAD ischemia had no effect on either the ESPLR slope or Lo. In contrast, the ESPLR slope in the LAD area was decreased by ischemia at I1 (-40%), increased at TO (+69%), and unchanged at CC and I2, and was reduced by diltiazem at CC and I2 (-31% and -36%, respectively). The LAD ESPLR Lo was increased by ischemia by 64% and 61% at I2, and 91% and 122% at TO, before and after diltiazem, respectively. In the LC region, diltiazem decreased systolic shortening and the ESPLR slope. These results indicate that diltiazem has negative inotropic properties in both ischemic and nonischemic areas. Also, Lo is not a constant and must always be redetermined for every intervention. In the absence of ischemia, the ESPLR may be a reliable measure of myocardial contractility.(ABSTRACT TRUNCATED AT 250 WORDS)