Biomedical subjects

J R Halliwill

Publications and source records attributed to J R Halliwill.

39 records · Page 3Linked to original sources

PubMed1993

The effects of the ATP-dependent potassium channel antagonist, glyburide, on coronary blood flow and susceptibility to ventricular fibrillation in unanesthetized dogs.

Extracellular potassium rapidly increases during myocardial ischemia and has been implicated in the development of ventricular fibrillation (VF). Recent evidence suggests that ischemically induced potassium efflux results from the opening of ATP-dependent potassium channels. If extracellular potassium accumulation contributes to VF, one would predict that drugs that block the ATP-dependent potassium channels should protect against these arrhythmias. Therefore, VF was induced in 15 mongrel dogs with healed myocardial infarctions by a 2-min coronary occlusion during exercise. This exercise (Ex) plus ischemia test consistently induced VF during each control (vehicle) presentation. However, glyburide, a sulfonylurea drug that selectively blocks the ATP-dependent potassium channel, prevented VF in 13 of 15 animals tested (p < 0.001, chi 2). Glyburide (G) elicited significant reductions in left ventricular dP/dtmax (Ex: control, 5,031 +/- 386.4; G, 3,286 +/- 116.6 mm Hg/s) and mean coronary blood flow (Ex: control, 49.6 +/- 8.7; G, 31.3 +/- 5.5 ml/min) both before and during exercise. The heart rate responses to exercise and coronary occlusion were also reduced. Since heart rate reductions could contribute to the cardioprotection, the exercise plus ischemia test was repeated with the heart rate held constant by ventricular pacing. Glyburide still protected four of five animals under these conditions. These data indicate that glyburide, a drug that blocks the ATP-dependent potassium channels, can prevent VF independently of changes in the heart rate. The data further suggest that these channels may contribute to the coronary vasodilation elicited by an increase in metabolic demand during exercise.

Adenosine Triphosphate↗

PubMed1993

Renal sympathetic responses to conflicting baroreceptor inputs: rapid ventricular pacing in dogs.

1. Ventricular tachycardia generates complex changes in baroreceptor input to the central nervous system: arterial baroreceptors are unloaded while cardiopulmonary receptors are stimulated. In humans with heart diseases, muscle sympathetic nerve activity increases during ventricular tachycardia. This suggests that arterial baroreceptor-mediated sympathoexcitation overrides cardiopulmonary receptor-mediated sympathoinhibition. However, the relative roles of each reflex are difficult to determine in humans. 2. We measured efferent renal sympathetic neural responses to simulated ventricular tachycardia, to determine what pathophysiological mechanisms are invoked when inputs from different baroreceptive areas change in opposite directions. In alpha-chloralose anaesthetized, mechanically ventilated dogs, we recorded the electrocardiogram, mean left atrial and arterial pressures and multifibre efferent renal sympathetic nerve activity (RSNA) during 1 min of right ventricular pacing at 214 beats min-1. Pacing was repeated after either sinoaortic or vagal cardiopulmonary denervation and again after both sinoaortic and cardiopulmonary denervation. 3. With all afferent baroreceptor pathways intact, right ventricular pacing elicited transient sympathoinhibition (delta RSNA, -19 +/- 10%, mean +/- S.E.M.). After sinoaortic denervation (cardiopulmonary receptors intact), right ventricular pacing elicited abrupt and sustained sympathoinhibition (delta RSNA, -53 +/- 8%, P < 0.05 vs. intact). After vagal cardiopulmonary denervation (sinoaortic receptors intact), right ventricular pacing elicited abrupt and sustained sympathoexcitation (delta RSNA, + 56 +/- 19%, P < 0.05 vs. intact). After both sinoaortic and vagal cardiopulmonary denervation, right ventricular pacing elicited a gradual increase in sympathetic outflow (delta RSNA, + 16 +/- 6%, P < 0.05 vs. intact). 4. We conclude that interactions between vagal cardiopulmonary and arterial baroreflexes determine renal sympathetic outflow during simulated ventricular tachycardia. In healthy anaesthetized dogs, the balance of the two opposing reflexes is weighted towards vagal cardiopulmonary-mediated sympathoinhibition.

Animals↗

PubMed1992

Effect of general anesthesia on cardiac vagal tone.

Although it is accepted that general anesthetics alter cardiac vagal tone, the magnitude of this effect was difficult to quantify by noninvasive methods until recently. Twenty-eight mongrel dogs were anesthetized using one of four representative anesthetics: pentobarbital sodium (25 mg/kg iv), morphine (1 mg/kg sc) with alpha-chloralose (50 mg/kg iv), urethan (500 mg/kg iv), thiopental sodium (25 mg/kg iv), and halothane (2% inhalation). Heart period (R-R interval) was recorded, from which the amplitude of the respiratory sinus arrhythmias (RSAs; frequency 0.24-1.04 Hz) was determined by time-series analysis. Morphine with alpha-chloralose-urethan significantly (P less than 0.01) increased RSA (control 8.3 +/- 0.6 ln ms2, anesthesia 9.4 +/- 0.3 ln ms2), whereas thiopental and halothane both significantly (P less than 0.01) decreased RSA (control 8.7 +/- 0.4 ln ms2, thiopental 1.3 +/- 0.4 ln ms2; and control 8.5 +/- 0.6 ln ms2, halothane 3.6 +/- 0.8 ln ms2). Pentobarbital failed to elicit a consistent change in RSA. These data suggest that vagal tone was maintained during morphine with alpha-chloralose-urethan anesthesia but was reduced during thiopental and halothane anesthesia.

Analysis of Variance↗