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Biomedical subjects

B M Graf

Publications and source records attributed to B M Graf.

44 records · Page 3Linked to original sources
PubMed1995

Isotonic versus hypertonic initial hyperkalemic reperfusion after cardioplegic arrest in isolated hearts.

In 24 isolated perfused guinea-pig hearts, 40 min of hyperkalemic arrest and ischemia at 37 degrees C were followed by 5 min of either isotonic or hypertonic initial hyperkalemic reperfusion (HKR). Hearts were divided into 3 groups: HKR, 5 min initial reperfusion with isotonic hyperkalemic Krebs' solution; Mannitol, initial reperfusion with hypertonic (450 mosm für 1 min and 330 mosm for 4 more min) hyperkalemic Krebs' solution modified by addition of mannitol; NaCl, same as Mannitol group but using NaCl instead of mannitol to increase osmolarity. In isotonic HKR hearts, postischemic peak reflow was 98 +/- 11% of pre-ischemic control. Subsequently coronary flow stabilized at 75% of control. Left-ventricular developed pressure (LVDP) recovered to 60% of control. Hypertonic reperfusion increased peak reflow to 141 +/- 11% in the mannitol and to 121 +/- 12% in the NaCl groups, but had no effect on the subsequent reduction of coronary flow to 75% of control. Recovery of LVDP, dP/dtmax, dP/dtmin, the time constant of relaxation, and O2 consumption did not differ between groups. Postischemic flow responses to adenosine, acetylcholine, and nitroprusside were equivalently reduced in all groups. We conclude that the flow increase seen in the hypertonic reperfusion model of the study may be due to direct coronary vasodilation rather than the desired reduction of endothelial or perivascular cell edema by the hypertonic solutions.

Animals↗
PubMed1995

The comparative effects of equimolar sevoflurane and isoflurane in isolated hearts.

The aim of this study was to compare the direct effects of equivalent molar concentrations of sevoflurane (SEVO) and isoflurane (ISO) on electrophysiology, mechanical function, metabolism, and perfusion in isolated hearts, independent of neuronal, humoral, or hemodynamic influences. Three equimolar concentrations of SEVO or ISO were administered randomly in each of 14 guinea pig hearts perfused by the Langendorff technique. Spontaneous heart rate (HR), atrioventricular (AV) conduction time, left ventricular pressure (LVP), and coronary flow (CF) were measured directly. To differentiate a direct vasodilatory effect from an indirect metabolic effect due to autoregulation of CF, arterial and coronary sinus oxygen tension were measured continuously to calculate oxygen delivery (Do2), myocardial oxygen consumption (MVo2), percent O2 extraction, and cardiac efficiency. Linear slope analysis (cardiac effect as a function of 0.1 mM anesthetic concentration) was used to compare anesthetic effects. Only AV time was increased more (P < 0.05) by ISO (+1.8 ms per 0.1 mM) than by SEVO (+1.1 ms per 0.1 mM). CF tended to be higher with ISO (+0.7 mL.g-1.min-1 per 0.1 mM) than SEVO (0.4 mL.g-1.min-1 per 0.1 mM) but this was not significant. HR (ISO, -1.4% per 0.1 mM; SEVO, -1.7% per 0.1 mM), LVP (ISO, -5.8% per 0.1 mM; SEVO, -5.1% per 0.1 mM), and percent O2 extraction (ISO, -6.1% per 0.1 mM; SEVO, -5.8% per 0.1 mM) were decreased similarly by both anesthetics and these effects were accompanied by proportional decreases in MVo2 (ISO, -34% +/- 4%, SEVO, -37% +/- 6%) at the highest concentrations (0.53 mM). Neither anesthetic altered cardiac efficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗
PubMed1995

Ketamine has stereospecific effects in the isolated perfused guinea pig heart.

BACKGROUND: S(+)-Ketamine is judged to produce more potent anesthesia than either the racemate or the R(-) ketamine isomer because of differential activation of specific cerebral receptors. Other than central nervous system effects, the most important side effects of ketamine occur in the cardiovascular system. We examined the direct cardiac effects of the isomers and the racemate of ketamine in the isolated perfused guinea pig heart. METHODS: Twenty-three guinea pig hearts were perfused by the Langendorff technique with modified 37 degrees C Krebs-Ringer's solution (97% oxygen and 3% carbon dioxide) at a constant perfusion pressure. Eight animals were pretreated with reserpine to deplete hearts of catecholamines. These pretreated hearts were also perfused with Krebs-Ringer's solution containing propranolol, phenoxybenzamine, and atropine to block any remaining effects of catecholamines and of acetylcholine. Five additional hearts were perfused with naloxone to block cardiac opioid receptors. Ten hearts were not treated. All 23 hearts were then exposed to four increasing equimolar concentrations of each isomer and the racemate of ketamine for 10 min. Heart rate, atrioventricular conduction time (AVCT), left ventricular pressure, coronary flow, and inflow and outflow oxygen tensions were measured. Percentage oxygen extraction, oxygen delivery, and oxygen consumption were calculated. RESULTS: Both isomers and the racemate caused a concentration-dependent depression of systolic left ventricular pressure and an increase in AVCT. In the untreated hearts, S(+)-ketamine decreased heart rate and left ventricular pressure and, at higher concentrations, oxygen consumption and percentage oxygen extraction significantly less than R(-)-ketamine independent of blocked or unblocked opioid receptors. Racemic ketamine depressed cardiac function to a degree intermediate to that produced by the isomers. Coronary flow and AVCT were equally affected by the isomers and by the racemic mixture. In the catecholamine-depleted hearts both isomers and the racemate caused equipotent depression of all variables. In these hearts cardiac depression was greater, and AVCT, coronary flow, and oxygen delivery were significantly greater than in untreated and opioid receptor-blocked hearts. CONCLUSIONS: Lesser cardiac depression by the S(+) isomer is attributable to an increased availability of catecholamines, because previous depletion of catecholamine stores and autonomic blockade completely inhibited these differences. The inability of cardiac tissue to reuptake released catecholamines into neuronal or extraneuronal sites during exposure to ketamine is stereoselective and caused predominantly by the S(+) isomer. Cardiac opioid receptors are apparently not involved in this phenomenon.

Animals↗
PubMed1995

One-day hypothermic preservation of isolated hearts with halothane improves cardiac function better than low calcium.

BACKGROUND: Halothane exerts a potent negative inotropic effect on the heart and mimics many of the cardiac effects of lowered extracellular CaCl2. Reduced slow inward Ca2+ current and sarcoplasmic reticular effects on intracellular Ca2+ are likely involved. The authors reported previously that halothane protects against hypoxic and ischemia reperfusion injury in isolated hearts. The aim of this isolated heart study was to compare protective effects of halothane and low CaCl2 (0.5 mM) administered during 1 day of hypothermic perfusion on return of normothermic perfusion. METHODS: Guinea pig hearts (n = 66) were isolated and perfused at 37 degrees C with a Krebs' solution, gassed with 96% O2, 4% CO2, and containing 2.5 mM Ca2+, and 4.5 mM K+. Heart rate, isovolumetric left ventricular pressure, coronary flow, %O2 extraction, O2 consumption rate, and relative cardiac efficiency (EFF = heart rate.left ventricular pressure/O2 consumption rate) were measured in five groups of hearts: time controls (no hypothermia); 1.5, and 3% halothane delivered by vaporizer; cold controls (hypothermia only); and 0.5 mM CaCl2. Halothane was administered, or CaCl2 was decreased 0.5 h before hypothermia at 3.8 +/- 0.1 degrees C, during hypothermia for 22 h, and for 0.5 h after rewarming to 37.0 +/- 0.1 degrees C. Hearts were perfused at 25% of initial coronary flow during hypothermia. RESULTS: All groups had similar ventricular function and vasodilator responses before hypothermia. During normothermic reperfusion after hypothermia, both concentrations of halothane protected better than low CaCl2. Values, expressed as a percent of initial values in the five groups (time control, 3% halothane, 1.5% halothane, cold control, and 0.5 mM CaCl2, were respectively: 90 +/- 6, 54 +/- 6*, 48 +/- 5*, 27 +/- 8, 27 +/- 4% for left ventricular pressure; 84 +/- 5, 61 +/- 4*, 62 +/- 6*, 40 +/- 5, 34 +/- 5% for EFF; and 102 +/- 3, 63 +/- 3*, 66 +/- 3*, 55 +/- 2, 42 +/- 2% for coronary flow (*P < 0.05 halothane vs. 0.5 mM CaCl2). The coronary flow response to endothelium-dependent (acetylcholine) and endothelium-independent (nitroprusside) vasodilators was also greater after halothane than after 0.5 mM CaCl2. CONCLUSIONS: Halothane administered during hypothermia restores left ventricular pressure, cardiac efficiency, basal coronary flow, and flow responses better than low CaCl2. Although halothane and low CaCl2 both reduce intracellular Ca2+, contractile force, and metabolic demand, the better protective effect of halothane is not likely simply due to a reduction in contractile function and metabolic rate before or initially after hypothermia because these were reduced much more by low CaCl2 than by halothane.

Anesthetics↗
PubMed1994

Lack of stereospecific effects of isoflurane and desflurane isomers in isolated guinea pig hearts.

BACKGROUND: Volatile anesthetics alter membrane channel proteins. It is controversial whether they act by nonspecifically perturbing lipid membranes or by directly binding to amphiphilic and usually stereoselective regions on channel macromolecules. Biologically relevant receptors are usually stereoselective. The stereochemical effect of isoflurane and desflurane can be used as a pharmacologic tool to investigate whether these drugs bind to specific target sites. The specific optical isomers of isoflurane and desflurane were used to examine whether they produce any differential effects on electrical, mechanical, and metabolic function in isolated hearts. METHODS: Isolated guinea-pig hearts were perfused with Krebs-Ringer's solution containing, in random order, both isomers of either isoflurane (n = 11) or desflurane (n = 6) for 10 min with a 15-min washout period. Either anesthetic was injected into a preoxygenated, sealed bottle of perfusate, which gave concentrations of 0.28 and 0.57 mM for isoflurane and 0.48 and 0.88 mM for desflurane, which are equivalent to 1 and 2 MAC multiples. RESULTS: Both isomers of isoflurane and desflurane decreased left ventricular pressure, heart rate, and percent oxygen extraction and increased atrioventricular conduction time, coronary flow, and oxygen delivery. Each change was significantly different from control at each concentration, and these effects were greater with the high compared to the low concentration of each anesthetic. There was no significant difference between the (+)- and the (-)-isomers for either anesthetic for any measured or calculated variable. Also, the effects of the stereoisomers were similar to those of the racemic mixture. CONCLUSIONS: These data indicate that the optical isomers of isoflurane and desflurane are equipotent, as assessed by their effects on cardiac function in isolated guinea-pig hearts. Although both agents may ultimately influence hydrophilic domains of the protein channels, their major cardiac effect appears to result either from global perturbation of the membrane lipids and/or an interaction at nonstereoselective sites on channels modulating cardiac anesthetic effects.

Animals↗
PubMed1994

Contraction uncoupling with butanedione monoxime versus low calcium or high potassium solutions on flow and contractile function of isolated hearts after prolonged hypothermic perfusion.

BACKGROUND: Normal ionic perfusate containing butanedione monoxime (BDM), a reversible myofilament inhibitor, could be better than either a high potassium (KCl) or a low calcium (CaCl2) perfusate for long-term cardiac preservation. This hypothesis was tested in 70 isolated guinea pig hearts. METHODS AND RESULTS: Three groups--time control (8 hours, 37 degrees C), cold control (22 hours, 3.8 degrees C), and cold+BDM (22 hours)--were perfused with typical Krebs-Ringer solution (2.5 mmol/L CaCl2 and 4.5 mmol/L KCl). Two other groups were cold perfused for 22 hours either with 2.5 mmol/L CaCl2 + 20 mmol/L KCl (high) or with 0.5 mmol/L CaCl2 (low) + 4.5 mmol/L KCl. These changes were maintained from 20 minutes before cold perfusion until 30 minutes after rewarming to 37 degrees C. Coronary vasodilator reserve was tested before cold perfusion and 2 hours after warm reperfusion with adenosine (Ade), acetylcholine (Ach, endothelium dependent), and nitroprusside (NP, endothelium independent). Each treatment decreased left ventricular pressure (LVP) by more than 80% before cold perfusion. During warm reperfusion, LVP was lower in cold control (-72 +/- 5%), high KCl (-76 +/- 4%), and low CaCl2 (-80 +/- 4%) groups than in BDM (-38 +/- 3%) or time control (-18 +/- 4%) groups; coronary flow (CF) was lower in high KCl (-67 +/- 4%) and low CaCl2 (-54 +/- 7%) groups than in cold control (-37 +/- 6%), BDM (-30 +/- 5%), or time control (+2 +/- 3%) groups; and percent oxygen extraction (controls, 62 +/- 4%) was higher in the high KCl group (83 +/- 6%) than in cold control (72 +/- 3%), BDM (73 +/- 3%), low CaCl2 (72 +/- 5%), or time control (63 +/- 3%) groups. CF responses to Ade, Ach, and NP (+103 +/- 7%, +24 +/- 5%, and +34 +/- 5% before cold) were attenuated (+76 +/- 6%, +18 +/- 5%, and +23 +/- 4%) in the time control group (5 hours later), were reduced but present in the BDM group (+10 +/- 5%, -5 +/- 5%, and -5 +/- 5%), and were absent in both low CaCl2 and high KCl groups after 2 hours of reperfusion. CONCLUSIONS: Normal ionic BDM solution better preserves cardiac function and basal CF after prolonged cold perfusion than do cold control, high KCl, and low CaCl2 solutions. Vasodilatory capacity is markedly diminished after perfusion with either the high KCl or the low CaCl2 solution.

Animals↗
PubMed1990

[A fatal hypertensive reaction during anesthesia in a patient with acute subarachnoid hemorrhage].

We describe the case of a 55-year-old female patient who presented for clipping of cerebral artery aneurysm that had ruptured 8 h before. Anesthesia induction was uneventful. After adequate positioning of the patient, two injections of a saline solution containing ornipressin (POR 8) were given into the scalp. Before surgical incision the patient developed a hypertensive reaction with arterial blood pressure of 230/140 mm Hg and heart rate 140/min. Pharmacologic intervention decreased the blood pressure and heart rate to normal values within 4 min. Upon surgical opening of the skull, the dura was found to be extremely noncompliant, and the pupils became wide and nonresponsive to light. Acute rebleeding was diagnosed, and the patient was sent back to the intensive care unit without clipping of the aneurysm and was declared brain-dead 12 h later. A Cushing response following acute rebleeding and other factors that might have caused the hypertensive crisis are discussed in detail. Anesthetic agents and adjuncts are assessed in terms of their influence on intracranial pressure and their protective action on the brain. Special consideration is given to subcutaneous ornipressin injection, which is known to be associated with cardiovascular side effects. Deep neuroleptanesthesia is recommended as the anesthetic technique of choice for clipping of cerebral artery aneurysms. Antihypertensive agents without cerebrovascular side effects should be used to treat hypertensive reactions.

Anesthesia, Inhalation↗