PubMed Health⌕ Search

Biomedical subjects

S V Rendig

Publications and source records attributed to S V Rendig.

27 records · Page 2Linked to original sources

Isolated working rat heart perfusion with perfluorochemical emulsion Fluosol-43.

Isolated working rat hearts were perfused with the perfluorochemical emulsion Fluosol-43 to determine whether it would support prolonged, stable cardiac function. The perfluorochemical emulsion provides a controlled perfusate composition, relatively high oxygen capacity, and a colloid osmotic pressure that is similar to that of plasma. Electrically paced (325 beats/min) hearts were perfused for 6 h at 35 degrees C in a recirculating system. Hemodynamic and mechanical function of seven Krebs-Henseleit-perfused hearts declined significantly more than that of seven Fluosol-43-perfused hearts over the 6-h period. The percent of initial function remaining at 6 h for Krebs-Henseleit-perfused vs. Fluosol-43-perfused hearts was 70.3 +/- 5.0 vs. 95.4 +/- 1.1% (P less than 0.001) for left ventricular peak systolic pressure; 55.6 +/- 7.7 vs. 97.5 +/- 2.4% (P less than 0.001) for dP/dtmax; 27.1 +/- 7.2 vs. 60.6 +/- 5.2% (P less than 0.005) for cardiac output; 11.0 +/- 6.3 vs. 67.2 +/- 3.4% (P less than 0.001) for external work efficiency; and 17.4 +/- 8.4 vs. 67.7 +/- 4.5% (P less than 0.001) for stroke rhythmic than Fluosol-43-perfused hearts during the last 3 h of perfusion. Perfusate lactate concentration was 4.5-fold higher in the Krebs-Henseleit perfusate than in the Fluosol-43 perfusate at 6 h, reflecting greater anaerobic metabolism in the Krebs-Henseleit-perfused hearts. Thus isolated rat hearts perfused with Fluosol-43 have greater maintenance of hemodynamic and mechanical function over a longer time period than hearts perfused with Krebs-Henseleit bicarbonate buffer.

Animals↗

Comparative cardiac contractile actions of six narcotic analgesics: morphine, meperidine, pentazocine, fentanyl, methadone and l-alpha-acetylmethadol (LAAM).

Cardiac muscle contractile responses to six narcotic analgesics (morphine, meperidine, pentazocine, fentanyl, methadone and l-alpha-acetylmethadol), at concentrations from 10(-8) to 10(-4) M, both in the presence and absence of the narcotic antagonist, naloxone, were studied in the isolated, isometric cat right ventricular papillary muscle preparation. Measurements of maximum developed tension (T), maximum rate of tension development (dT/dt) and time to peak tension indicated that no major changes in contractile function occurred with any narcotic at concentrations of 10(-8) to 10(-6) M except for small but significant (P < .05) increases in all three parameters at 10(-6) M fentanyl, and small but significant increases in dT/dt at 10(-8) to 10(-6) M meperidine. At 10(-5) M narcotic, dT/dt was significantly elevated in meperidine-treated muscles (+7%), but significantly reduced in muscles exposed to pentazocine (-8%) or l-alpha-acetylmethadol (-11%). For all six narcotics, the 10(-4) M drug concentration resulted in depression of contractile function that was often associated with nonresponsiveness to electrical stimulation. Pretreatment of muscles with naloxone (10(-4) M) did not prevent this reduction of contractile performance except at the highest concentration (10(-4) M) of meperidine. Following removal of drug, contractile performance improved to varying degrees (recovery to 72-97% of control T), except in l-alpha-acetylmethadol-treated muscles, in which there was no recovery of T. Isoproterenol (0.8 X 10(-7) M) elicited a positive inotropic response whether administered in the presence of 10(-4) M narcotic or following narcotic removal. We conclude that narcotic analgesics in high concentrations exert a direct myocardial depressant effect which is not prevented by naloxone and therefore is not mediated by interaction with opiate receptors. Rather, several effects, including myocardial depression, its reversibility by both drug removal and isoproterenol and decreased muscle excitability are consistent with the hypothesis that narcotic analgesics in high concentrations exert nonspecific, local anesthetic effect on the myocardium.

Analgesics, Opioid↗

Left ventricular dysfunction of isolated working rat hearts after chronic alcohol consumption.

The mechanical, haemodynamic, and energetic functions of isolated perfused working hearts from chronic alcoholic and control rats were studied. Male Long-Evans rats were fed a nutritionally-complete liquid diet containing 38% of daily calories as ethanol (isocaloric replacement with dextrin-maltose for controls) for 34 to 48 weeks. Alcoholics and controls received either 7.4% (low-fat) or 21.0% (high-fat) of calories from lipid. Animals were matched by dry heart weight for comparisons and hearts were evaluated at a constant heart rate in an improved isolated ejecting heart perfusion preparation. Ventricular function curves and the response to 10(-7) mol . litre-1 dobutamine HCl were obtained during normoxic and hypoxic perfusion. In normoxia, the hearts from the high- and low-fat alcoholic animals exhibited a significantly lower response of left ventricular maximum systolic pressure, left ventricular maximum rate of pressure rise and maximum ejection velocity to dobutamine than did the controls. In hypoxia, the left ventricular maximum systolic pressure of the low-fat alcoholic hearts was slightly, but significantly, lower than that of the low-fat control hearts at the three filling pressures studied. Also in hypoxia, the increase in left ventricular maximum rate of pressure rise with dobutamine was significantly less in the alcoholic hearts than in controls. These data suggest that long-term consumption of moderate amounts of alcohol even along with a nutritionally-adequate diet can result in depressed myocardial contractility and pump function that may be manifest when the heart is subjected to stress conditions.

Animals↗

Effects of chronic graded ethanol consumption on the metabolism, ultrastructure, and mechanical function of the rat heart.

Three sequential sets of ethanolic rats (E) and their matched controls (C) were fed regular chow containing standard vitamins with the ethanol group in each series also receiving a progressively greater alcohol intake for 3 to 6 months: E1 5%, E2 10%, and E3 25% ethanol. Electron microscopy showed swelling of mitochondria, transverse tubules and sarcoplasmic reticulum, dehiscence of intercalated discs and disintegration of myofibrils scattered throughout the ventricular myocardium in E1 and E2 as early as 7 wk after beginning 5% ethanol; in addition, there were clumping of mitochondria and supercontraction of myofibrils in E3. Concomitant with substructural abnormalities in E3, there were slight but significant depressions of cardiac myofibrillar ATPase activity and mitochondrial function. Cardiac catecholamines, hydroxyproline, and total bound glycerol were unchanged. Alteration of isometric contraction of isolated, supported left ventricular papillary muscles occurred initially in E2 and was clearly evident in E3 by significant reduction of duration of systolic active state (time from onset to peak tension), while total tension generated and peak rate of tension rise were not yet disturbed. Extra vitamin supplementation in additional rats drinking 25% ethanol minimally lessened decline in myofibrillar ATPase activity, but otherwise provided no protection. Thus, chronic daily ingestion of graded quantities of ethanol representing 10 to 30% of total calories in well-nourished animals exerted toxic effects on microstructure, metabolism and mechanics of the ventricle. These alterations are postulated to be pertinent to early pathogenesis of clinical alcoholic cardiomyopathy.

Adenosine Triphosphatases↗

Positive inotropic action of amrinone: effect of elevated external Ca2+.

To investigate the positive inotropic effect of amrinone under conditions of maximal contractile stimulation, we compared cumulative amrinone one-half log dose-response curves (dose range, 3.1 X 10(-5)-3.1 X 10(-3) M amrinone) of isolated cat right ventricular papillary muscle in normal (2.5 mM) and high (7.5 mM) calcium Krebs solution. In 2.5 mM calcium, amrinone induced significant (p less than 0.01) dose-dependent increases in peak developed tension (T), maximum dT/dt, and maximum relaxation rate (-dT/dt), which were accompanied by small but significant decreases in time-to-peak tension (TTP). At 10(-3) M, changes in T, dT/dt, and TTP were 61.9 (2.7 g/mm2), 98.1 (33.2 g/s/mm2), and -13.1% (-26 ms), respectively. In 7.5 mM calcium, the increases in T, dT/dt, and -dT/dt, and the reduction of TTP, were markedly less at each concentration. At 10(-3) M amrinone, T and dT/dt increased significantly by 16.7 (1.3 g/mm2) and 23.5% (17.4 g/s/mm2), respectively, with no change in TTP. The amrinone-induced reductions in one-half relaxation time and twitch duration persisted in high calcium and were similar in magnitude to those in 2.5 mM calcium. The substantial reduction of amrinone's positive inotropic effect in high Ca2+ suggests that a major part of the drug's action involves an augmentation of contractile Ca2+. An amrinone-induced effect on rate of Ca2+ delivery to the contractile apparatus or on myofilament Ca2+ sensitivity would be consistent with a persistent inotropic action in high Ca2+. Contractile changes induced by amrinone are discussed in relation to a possible effect on intracellular cyclic AMP levels.

Aminopyridines↗

Sodium pentobarbital effects on cardiac function and response to dobutamine.

This study was undertaken to determine if sodium pentobarbital had persistent effects on isolated working rat heart function that altered the response of the heart to subsequently administered dobutamine. The effects of in vitro sodium pentobarbital treatment were studied using isolated working hearts from rats that were killed after pentobarbital anesthesia or by cervical fracture. Hemodynamic and contractile functions of the isolated hearts were significantly depressed in the presence of 0.4 mM sodium pentobarbital in vitro. After the pentobarbital was washed out of the preparation, all indices of cardiac function recovered fully except for -dP/dtmax, which remained depressed by approximately 7%. The subsequent inotropic response of the hearts to 5 X 10(-8) M dobutamine was minimally affected by the prior exposure to pentobarbital in vitro. The data confirmed that hearts from rats killed by cervical fracture exhibited a smaller inotropic response to dobutamine than hearts from pentobarbital-anesthetized rats. In addition, hearts excised from ventilated animals had significantly higher left ventricular peak systolic pressure, peak aortic flow rate, and peak power than hearts from nonventilated animals, indicating the importance of ventilating the animal during cardiac excision in order to obtain optimum isolated heart function.

Anesthesia↗