Acid-base, plasma lactate and glucose changes in the rabbit following administration of Gaboon viper (Bitis gabonica) venom.

The acid-base and metabolic effects of Bitis gabonica venom administered intravenously to the anaesthetised rabbit were studied. Doubling doses of venom from 0.125 mg/kg to 1.0 mg/kg were used. Venom caused progressive and significant increases in plasma glucose and plasma lactate levels although oxygen consumption only became significantly lower after the fourth dose. Standard base excess (SBE) became significantly more negative after the third dose of venom and the fall in pH became significant at the same point. The results indicate that venom induces a metabolic acidosis in the rabbit and because the acidosis occurs in the absence of any fall in arterial PO2, it cannot be considered a consequence of impaired pulmonary ventilation. The reduction in oxygen uptake is likely to occur at a cellular level with a shift from aerobic to anaerobic metabolism hence the increase in plasma lactate levels. However, the magnitude of the acidosis is unlikely to be the principal cause of death under experimental conditions.

The mechanical and electrical effects of rhinoceros viper (Bitis nasicornis) venom on the isolated perfused guinea pig heart and atrial preparations.

The mechanical and electrical effects of the venom of Bitis nasicornis were studied on the guinea-pig Langendorff and left atrial myocardium preparations. While Langendorff preparations were treated with individual doses of 0.1, 0.6 and 1.4 mg, isolated left atria were treated using concentrations of 2.0, 20 and 200 micrograms/ml of venom in the perfusion solution. In the Langendorff preparation, transient increases in left ventricular systolic pressure (LVSP) and heart rate (HR) were seen after 0.1 mg of venom. When 0.6 mg of venom was given, the increases were followed by decreases, while 1.4 mg doses simply induced decreases in LVSP and HR. After both 0.6 and 1.4 mg doses the decreases were accompanied by increases in left ventricular diastolic pressure. In addition to these mechanical effects, transient increases in HR with atrio-ventricular blocks, ventricular extrasystoles and tachycardia were observed after each dose. In the left atrium the 2 micrograms/ml venom concentration produced an increase, followed by a decrease, in the maximum tension developed, which was only seen to decrease with higher concentrations of 20 and 200 micrograms/ml of venom. A dose dependent significant reduction in the action potential duration was observed for the doses of 0.6 and 1.4 mg in the ventricle and for all three concentrations in the atrium.

[Ventricular volume and coronary flow]. / Volume ventricolare e flusso coronarico.

This study aimed at investigating the role of ventricular volume (VV), left ventricular pressure (LVP) and myocardial contractility in causing changes in coronary flow (CF), in the absence of autoregulation. Changes in VV and, consequently, in LVP and myocardial contractility were induced in 5 anesthetized dogs using an extracorporeal circulation including a heart-lung machine. Left VV was changed in steps of 10 ml, from a lowest value of 10 ml to a maximum value of 70 ml and back, by introducing and subtracting different volumes of water in and from a latex balloon placed in the left ventricle. In order to suppress any interference by autoregulatory mechanisms, the experimental manoeuvres were performed in the presence of complete coronary vasodilation obtained with dipyridamole. Each increase in VV was accompanied by an increase in diastolic LVP which was in turn responsible for a greater development of pressure by the myocardial contraction, thus producing an increase in systolic LVP. Then, the pressure developed by the myocardial contraction, considered as the difference between systolic and diastolic LVP, decreased when the ventricle was dilated to 60 and 70 ml. Diastolic CF decreased only starting from a ventricular volume of 60 ml, varying independently of the changes in diastolic LVP. In addition, the amplitude of the coronary flow reduction in systole was found to change together with the pressure developed by the myocardial contraction with which showed a significant linear correlation. During the reduction in VV, a progressive fall of diastolic LVP occurred without any significant difference with respect to the phase of increased volumes; on the contrary, systolic LVP, at each ventricular volume, was lower than in the previous phase. Also diastolic CF, when the volume was progressively reduced, was lower than in the previous manoeuvre. The amplitude of the systolic flow reduction and the pressure produced by the contraction both decreased when the ventricular volume was reduced showing a significant linear correlation. The reduction of the pressure produced by the contraction is likely to be due to a loss of contractility after the ventricle was expanded more than 3 times its resting volume. It is concluded that changes in ventricular pressure do not influence phasic CF directly and that diastolic CF decreases only following extreme ventricular dilation. Finally, systolic flow reduction is seen to depend on the myocardial contractility and not on the levels reached by the pressure inside the ventricle.

The primary reflex effects of distension of the stomach on heart rate, arterial pressure and left ventricular contractility in the anaesthetized pig.

The present study was planned to investigate whether distension of the stomach primarily affects the heart rate, arterial blood pressure and left ventricular inotropic state and to explore the reflex mechanisms involved. In 16 anaesthetized pigs, distension of gastric balloons with 0.81 of Ringer solution (gastric transmural pressure of about 13 mmHg) without controlling any haemodynamic variable caused an increase in arterial blood pressure. When this response was prevented, an increase in heart rate was obtained in each animal. In five pigs, the increase in heart rate was graded by step increments of distension. No significant changes in maximum rate of change of left ventricular pressure were observed in the sixteen pigs during gastric distensions performed whilst preventing changes in heart rate and arterial blood pressure. The responses of arterial blood pressure and heart rate were not influenced by the administration of atropine (four and six pigs respectively), while they were abolished by the administration of bretylium tosylate (ten pigs) and by bilateral vagotomy (six pigs; three cervical, three subdiaphragmatic). The present study showed that gastric distension which was likely to be innocuous in the anaesthetized pig reflexly increased arterial blood pressure and heart rate. The afferent limb of the reflex was in the vagal nerves and the efferent limb involved sympathetic pathways.

The effect of distension of the stomach on coronary blood flow in anaesthetized pigs.

The present study was undertaken in anaesthetized pigs to determine whether distension of the stomach reflexly affects coronary blood flow. Experiments were performed on 17 pigs anaesthetized with ketamine and sodium pentobarbitone and artificially ventilated. Coronary blood flow was measured with an electromagnetic flowmeter positioned around the origin of the left circumflex coronary artery. The stomach was distended by injecting 0.8l warm Ringer solution into a balloon positioned within the stomach (mean gastric transmural pressure of about 13 mm Hg). Changes in aortic blood pressure and heart rate were prevented by a pressurized reservoir connected to the left femoral artery and by atrial pacing respectively. Distension of the stomach always caused a decrease in mean coronary blood flow. In five pigs, the magnitude of the decrease in coronary blood flow was graded by step increments in the gastric distending volume from 0.6l to 1l. The response of coronary blood flow was not affected by the administration of atropine (12 pigs), while it was abolished by the administration of bretylium tosylate (eight pigs) and by bilateral vagotomy (eight pigs; four cervical, four subdiaphragmatic vagotomy). These results show that innocuous distension of the stomach in anaesthetized pigs reflexly decreases coronary blood flow. This reflex response is mediated by sympathetic effects and its afferent limb involves the vagal nerves.

The haemodynamic effect of Bitis nasicornis (rhinoceros horned viper) venom.

1. Intravenous venom (0.0625 mg/kg) in the dog caused an immediate increase in coronary blood flow due to a fall in coronary vascular resistance (CVR). 2. Subsequently, total peripheral resistance (TPR) fell causing a significant reduction in aortic blood pressure (ABP). 3. CVR and TPR returned to normal after 20 min but ABP did not recover completely. 4. The failure of ABP to recover was due to decreased stroke volume and cardiac output (CO). 5. Animals died after four doubling doses of venom following irreversible reductions in CO, ABP and coronary flow.

Coronary myogenic responses to abrupt changes in aortic blood pressure in anaesthetized dogs.

A transient increase in coronary transmural pressure was produced in anaesthetized dogs by occlusion of the descending thoracic aorta. Aortic blood pressure (ABP), left ventricular pressure and coronary flow were measured; coronary vascular resistance (CVR) was calculated. Results were similar in innervated and denervated hearts. Occlusion for 10 and 20 s resulted in no change in CVR for 15 s, followed by a metabolic dilatation attributable to enhanced oxygen demand; after release the fall in ABP resulted in an immediate increase in CVR, caused by vascular elastic recoil, followed by hyperaemia.

Acidotic effect of gaboon viper (Bitis gabonica) venom in the urethane-anaesthetized rat.

1. Intravenous venom (4 mg/kg) caused a non-compensated metabolic acidosis. 2. Bicarbonate concentration, base excess, standard base excess and pH all fell dramatically. 3. A respiratory impairment occurred characterized by pulmonary oedema and a fall in arterial pO2. 4. Acidosis occurred soon after venom when pO2 was still normal, indicating that changes in tissue metabolism contributed to the acidosis independently of reduced oxygen availability.

The mechanical effects of rhinoceros horned viper (Bitis nasicornis) venom on the isolated perfused guinea-pig heart.

In the guinea-pig Langendorff heart preparation, addition of 0.1 mg Bitis nasicornis venom to the perfusion solution caused transient increases in heart rate (HR) and left ventricular systolic pressure (LVSP) with peak increases at 2 min. With higher doses (0.6 and 1.4 mg), these increases were followed by the return of HR to normal, significant decreases in LVSP below control values and marked increases in left ventricular diastolic pressure. Histaminergic blockade with ranitidine reduced the positive responses. The results suggest that a venom component, possibly acting on intracellular calcium movement, could be responsible for both positive and negative effects.

Coronary response to transient increases in transmural pressure.

Previous studies have shown that transient increases in aortic blood pressure obtained by occlusion of the descending thoracic aorta, in anesthetized dogs with beta-blockade and vagal section, did not affect coronary vascular resistance apart from a non-significant increase just after release of the constriction. The present study examined whether this response also occurred in the normally innervated heart. Experiments were carried out in six anesthetized dogs, in which pressure in the aortic root and in the left ventricle, as well as flow in the left circumflex coronary artery, were recorded. Coronary vascular resistance was calculated as the ratio of the difference between aortic pressure and left ventricular pressure to coronary circumflex flow during the slow inflow phase. Before occlusion coronary vascular resistance was significantly lower than during the same period in the previous studies using animals with beta-blockade and vagal section. During the occlusion, in contrast with the previous investigation, the increase in aortic pressure caused a significant increase in coronary vascular resistance 10 seconds after the beginning of the occlusion. Coronary vascular resistance was further increased immediately after release of the occlusion, concomitantly with the decrease in aortic pressure, which fell abruptly below the control level. The increase immediately after the release of the constriction was qualitatively similar, but greater in extent, to that observed in the animals with vagal section and beta-blockade. These differences are assumed to depend on a lower vasomotor tone in the normally innervated hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of tachycardia and constriction of left circumflex artery on coronary flow and pressure in anaesthetized dogs.

1. The effect of graded changes in heart rate between 100 and 160 beats/min and constriction of the left circumflex coronary artery which reduced coronary blood flow was examined in seven anaesthetized and artificially ventilated dogs in the absence of significant changes in aortic blood pressure. Mean diastolic coronary blood flow, and the difference between the mean diastolic pressures in the coronary artery and the left ventricle were related to the increase in heart rate. 2. In all seven dogs diastolic coronary blood flow showed linear increases with heart rate increments with and without coronary narrowing which averaged 70 and 82% respectively. 3. A significant shift to the right in the relation between heart rate and mean diastolic coronary blood flow occurred with each grade of coronary constriction. Coronary blood flow became lower at any given heart rate. 4. The shift to the right in the relation between heart rate and coronary blood flow was associated with decreases in the difference between the mean diastolic pressures in the coronary artery and the left ventricle which accompanied the increase in heart rate. 5. The results suggest that increases in heart rate can enhance diastolic coronary blood flow despite coronary narrowing which reduced flow, possibly through dilatation in myocardial blood vessels.

Mesangiolysis and endothelial lesions due to peroxidative damage in rabbits.

There is much evidence that oxygen free radicals (OFR) may be the final mediators of biochemical and molecular damage in many kidney diseases of different etiology (toxic, ischemic and immunologically mediated), involving mainly endothelium, basement membrane and tubular cells, but direct demonstration of a role in inducing mesangiolysis is lacking. An experimental model of renal damage caused by OFR was carried out in 6 rabbits using a mixture of xanthine-oxidase and xanthine, which produces a large amount of the radical superoxide anion. Both enzyme (0.0150 and 0.150 U/ml) and substrate (0.2 and 2 mM) were simultaneously infused in one kidney, while the controlateral kidneys perfused with buffer only were used as controls. Treated kidneys were compared to controls by light and electron microscopy. A further experiment was carried out in 4 other rabbits to evaluate the protection afforded by superoxide dismutase, the specific enzyme-scavenging superoxide anion. Microscopic studies showed dose-related ingravescent damage in the treated kidneys: capillary enlargement, subendothelial swelling, detachment of the endothelium from the basement membrane, mesangiolysis and microaneurysms. Control kidneys appeared to be normal. No significant differences were observed in the kidneys treated with addition of superoxide dismutase. These results are the first direct demonstration of a role of superoxide anion in the induction of mesangiolysis in rabbits. The lack of a protective effect by superoxide dismutase could mean that the superoxide anion triggers a chain of other OFR, further responsible for damage.