Evaluation of myocardial contractility in the chronically instrumented dog with intact autonomic nervous system function: effects of desflurane and isoflurane

Characterization of changes in myocardial contractility using indices derived from ventricular pressure-segment length loops in animals with intact autonomic nervous system (ANS) function is complicated by alterations in systemic hemodynamics mediated by baroreceptor reflexes and by spontaneous respiration and its effects on ventricular pressure and filling. This investigation examined and compared the effects of desflurane and isoflurane on myocardial contractility in dogs with intact ANS reflexes using techniques designed to overcome these potential difficulties. Two groups comprising 18 experiments were performed using nine dogs chronically instrumented for measurement of aortic and left ventricular pressure, the maximum rate of increase of left ventricular pressure (dP/dt), subendocardial segment length, cardiac output and intrathoracic pressure. A brief occlusion of the inferior vena cava was used to alter preload to generate pressure-length loops prior to onset of baroreceptor reflex-mediated increases in heart rate. Respiratory variation in ventricular pressure was negated by calculation of “transmural pressure” via instantaneous subtraction of intrathoracic pressure from corresponding left ventricular pressure. Contractility was then evaluated in the conscious and anesthetized states using transmural pressure-length loops and calculation of the preload recruitable stroke work (PRSW) relationship. Dogs were anesthetized with 1.25, 1.5, or 1.75 MAC desflurane or isoflurane and measurements were repeated after 30 min of equilibration at each anesthetic concentration. Desflurane and isoflurane produced similar declines in PRSW slope [M_w; 41±6 (5.5 ±0.8) during 1.75 MAC desflurane compared to 43 ± 5 mmHg (5.7 ± 0.7 kPa) during 1.75 MAC isoflurane], indicating that these agents cause similar depression of contractile state at equivalent MAC. The PRSW relationship derived from transmural pressure-length loops using brief inferior vena caval occlusion may facilitate the examination of the impact of other volatile and intravenous anesthetics on myocardial contractility using a load-independent index of contractile state in the presence of intact ANS reflexes.     

Downregulation of myocardial contractility via intact ventriculo--arterial coupling in the brain dead organ donor.

OBJECTIVE: To test the hypothesis that altered loading conditions play a key role in hemodynamic instability and cardiac dysfunction in the brain dead (BD) organ donor. METHODS: BD was induced by inflation of a subdural balloon catheter. In the first part of the study, left ventricular function was assessed in a canine in situ cross-circulated heart model (n=6). Pre- and afterload and coronary perfusion pressure were kept identical in all hearts throughout the experiment. In the second part of the study, hearts (n=6) were investigated in vivo allowing the interaction between left ventricular contractility and arterial load. Left ventricular pressure--volume loops were obtained by a combined conductance-pressure catheter and the slope of the endsystolic pressure--volume relationship (Ees), arterial elastance (Ea), stroke work (SW), pressure--volume area, ventriculo--arterial coupling ratio (VAC) and mechanical efficiency (Eff) were calculated. RESULTS: Induction of BD led to a hyperdynamic response in both models with a significant increase of most hemodynamic parameters. In the in situ isolated heart model, left ventricular contractility returned to baseline without any further deterioration. In contrast, in the intact circulation the hemodynamic parameters declined significantly in comparison to baseline 4 h after BD (Ees: 4.07+/-0.51 vs. 8.06+/-1.09 mmHg/ml, P<0.05, Ea: 3.17+/-0.39 vs. 4.42+/-0.30 mmHg/ml, P<0.05). However, VAC (0.78+/-0.09 vs. 0.65+/-0.14 n.s.) and Eff (73.4+/-2.1 % vs. 76.8+/-3.7 %, n.s.) remained constant over the time. CONCLUSION: BD induction leads to an initial hyperdynamic reaction followed by hemodynamic instability. The facts that no cardiac dysfunction occurred if loading conditions were kept constant and the ventriculo--arterial coupling ratio and mechanical efficiency remained constant in the intact animal model indicate that decreased contractility reflects to decreased arterial elastance after brain death. Therefore, reduced contractile function after brain death at a decreased afterload may contribute to stroke work optimization.     

The influence of meperidine and nitrous oxide on respiratory depression in rats.

Narcotic sedation is commonly accomplished with nitrous oxide (N2O) coadministration. Concerns regarding respiratory morbidity and mortality with drug combinations have been reported in the literature, particularly in patients not receiving supplemental oxygen (O2). The purpose of this investigation was to determine the effect of meperidine alone and in combination with N2O on respiration in laboratory rats by evaluating cardiovascular and arterial blood gas data. Fifty-four Sprague-Dawley rats were assigned to one of six groups (nine per group). Groups were allocated based upon the dosage of meperidine administered (0, 4.0, or 8.0 mg/kg intraperitoneally [i.p.]) and exposure to N2O (50% with oxygen) or O2 (100%). Following meperidine administration, animals were placed into a sealed chamber through which flowed either N2O or O2. Arterial blood was obtained, at baseline and at 15-min intervals, from a femoral artery catheter and pH, O2, CO2 (mm Hg), and oxygen saturation (%) were determined. Plasma samples were analyzed using a System 1306 pH/blood gas analyzer. Group comparisons demonstrated that: (a) N2O coadministration, in animals pretreated with meperidine, did not result in increased arterial CO2 levels, and (b) as expected, arterial O2 levels in all groups increased significantly from preexposure baseline values (P < 0.05). This investigation demonstrated that the coadministration of N2O to meperidine-sedated animals did not enhance respiratory depression.     

Effect of valproate on renal metabolism in the intact dog

Valproate is an antiepileptic drug known to induce hyperammonemia in humans. This hyperammonemia might result from a reduced detoxification of ammonium in the liver and/or from an accelerated renal ammoniagenesis. Six dogs with normal acid-base equilibrium and eight dogs with chronic metabolic acidosis were infused with valproate directly into their left renal artery in order to obtain arterial concentrations around 3 to 4 mM. The arterial ammonium concentration rose only in chronically acidotic dogs, whereas the lactate concentration and the lactate/pyruvate ratio increased in both groups. The urinary excretion of lactate and pyruvate increased markedly but the urinary excretion of other relevant metabolites remained minimal. Renal glutamine utilization and ammonium production were not changed by valproate administration in normal dogs but increased modestly in acidotic dogs. However, renal lactate utilization was drastically reduced and in fact, changed into a net production of lactate. Valproate strikingly reduced the renal cortical concentrations of glutamine, glutamate, alphaketoglutarate and citrate, and more modestly those of malate, oxaloacetate, aspartate, alanine and ATP. By contrast, the tissue lactate concentration and the lactate/pyruvate ratio were markedly increased. In experiments with brush border membrane vesicles, valproate inhibited the lactate transporter. These results suggest that high concentrations of valproate drastically inhibited the proximal reabsorption and the proximal and distal oxidation of lactate and pyruvate. Valproate probably became itself a significant energetic substrate for the kidney.     

Effects of portal vein occlusion on myocardial contractility

We studied canine left ventricular contractile performance following 15min of portal vein occlusion by analyzing the end-systolic pressure diameter relationship (ESPDR) which many investigators have reported as being independent of changes in preload and afterload but sensitive to changes in ventricular contractility. Portal vein occlusion for 15min decreased the mean arterial pressure, left ventricular peak systolic pressure, and cardiac index, while the release of the occlusion gradually increased these values, although it did not restore them to the control values. The systemic vascular resistance index increased during portal vein occlusion and returned to the control values after release. Left ventricular end diastolic diameter decreased during portal clamping and returned to the control values after release. ESPDR and percent shortening were not significantly changed during or after portal clamping. These rersults indicate that the decrease in blood pressure during portal vein occlusion was not due to a reduction in myocardial contractility but rather was due to a reduction in preload.(Oka T, Ohwada T, Mizuguchi T, et al.: Effects of portal vein occlusion on myocardial contractility. J Anesth 5: 344–351, 1991)     

The influence of changes in extracellular and intracellular sodium concentration on detrusor contractility

OBJECTIVE: To determine the role of Na+-Ca2+ exchange in the regulation of isolated detrusor smooth muscle contractility. MATERIALS AND METHODS: Isolated guinea-pig detrusor strips were used to record isometric tension generated by; (a) electrical-field stimulation to elicit nerve-mediated responses; and (b) adding carbachol or superfusing with a high-K+ solution. The [Na+] gradient between extracellular and intracellular compartments was altered by: (i) reducing superfusate [Na+] in stages from 140.2 to 10.2 mm; (ii) addition of the cardiac glycoside strophanthidin (200 microm). RESULTS Reducing extracellular [Na+] reversibly reduced the magnitude of nerve-mediated contractions but increased the resting tension and magnitude of carbachol-induced contracture. The mean (sd) [Na+] required for a half-maximum effect on attenuating contractions, at 85.9 (6.2) mm, and developing contracture, at 59.1 (14.3) mm, were significantly different. The time constants of changes to nerve-mediated contractions and carbachol contracture were also significantly different, at 147 (5) vs 1207 (386) s, respectively. These differences suggest that separate mechanisms influence nerve-mediated contraction and contracture in low-Na+ solutions. Exposure to the cardiac glycoside strophanthidin produced a similar effect to low-Na+ solutions for carbachol contracture. Low-Na+ solutions had no significant effect on contractures induced by high extracellular [K+]. CONCLUSION Reducing the transmembrane [Na+] difference increases intracellular [Ca2+]. This increase is largely accommodated in intracellular stores, that can be released by exogenous carbachol. The results are consistent with the presence of a functional Na+-Ca2+ exchanger in the surface membrane. The lack of effect of low-Na+ solutions on contractures evoked by membrane depolarization is consistent with this conclusion. The reduction of the nerve-mediated contraction by low-Na+ solution might result from blockade of the nerve action potential.