The effects of vasopressin (ADH) were tested on the cardiovascular system of 7 catheterized barbitone-anaesthetized beagle dogs.ADH, as a constant intravenous infusion for 10 min at 0.01 and 0.1 IU/kg/min, induced a dose-dependent increase of mean arterial blood pressure (MAP). At the higher dose there was a reversal of the effect 30 min after the primary increase. Similar changes were observed for left ventricular peak pressure (LVP).Heart rate (HR) and dP/dtmax showed a significant dose-dependent decrease, while total peripheral resistance (TPR) and the contraction period t-dP/dt showed a dose-dependent increase; all reaching their maximum alterations at the end of infusion, with a slow decline thereafter.Cardiac output index (COD was strongly reduced with clear dose-relationship, whereas stroke volume index (SVI) remained unaffected by the low dose and only showed a slight reduction at the higher dose. The parameter VeE was significantly reduced parallel to HR, while Vpm dropped at both doses with lesser significance.The time index t-Vpm consequently was elongated at the low dose. For the high dose there were two subsequent elevations with some similarity to the time course of MAP and LVP.Ejection time (ET) increased as did left ventricular end-diastolic pressure (LVEDP) and left ventricular end-systolic volume (LVESV). Dose-dependence was absent for the LVEDP elevation seen after discontinuing the infusion, and an inverse dose relationship occurred following the 30th rain for ET and the 45th min for both LVEDP and LVESV.Cardiac work (CW) declined in a dose-dependent manner. Left ventricular oxygen consumption (MVO2) was reduced for both doses with a lack of dosedependence following the infusion of the hormone.The antidiuretic hormone (ADH), a nonapeptide from the posterior pituitary with its site of action at the distal nephron, is also known as adiuretine or vasopressin. Its release can be stimulated by stress condi-905

Anesthetized spontaneously breathing rats, fitted with epicortical electrodes and catheters for sampling arterial, venous, and cerebral venous blood, were exposed to standardized progressive hypoxia. Three minutes of hypoxia sequentially caused hyperpnea, hypopnea, apnea, and cessation of electrocorticogram "spiking," of synchronization, and of background in electroencephalogram (EEG). Blood data and cerebral blood flow and metabolism were measured throughout and at "insults," i.e., at apnea and cessation events, to clarify their interdependence. Arterial and brain venous PO2 fell linearly with inspired oxygen (final value of 2% at 280 s). Hyperpnea induced arterial alkalosis; subsequent hypopnea led to near-normal PCO2 and pH when EEG ceased. Hypercapnia was more pronounced in cerebral than in systemic venous blood; time courses of pH changes were similar. Sagittal sinus blood pressure and outflow were linearly related and resembled the time course of local cerebral blood flow. Blood flow increased by 25% at apnea and only 60% at EEG silence. Cerebral metabolic rate of O2 rose during the hyperpnea phase and fell exponentially thereafter. Cerebral glucose uptake and lactate release increased within the first 3 min but fell abruptly when cortico-electric spiking ceased. Time courses of cerebral O2 consumption and spike rate were linearly related; both showed inverse linear relations to cerebral perfusion. The hypoxic insults were well defined by blood data; critical PO2 values were lower than previously assumed. This model is proving to be a useful, controlled method by which mechanisms of cerebral hypoxia tolerance may be studied in vivo.

No abstract

The protective effects of ten slow channel inhibitor drugs against severe progressive hypoxia were investigated in rats breathing spontaneously during light anaesthesia. Respiration, heart rate, electrocorticogram (ECoG) and/or electroencephalogram (EEG) were recorded. Tolerance times were monitored from hypoxia onset until cessation of respiration, ECoG, EEG synchronization, and ‘background‐EEG’. Drugs were administered i.v. 5 min before the onset of hypoxia. Verapamil, gallopamil, and nimodipine resulted in a significant increase of tolerance times; fendiline and bepridil showed a small increase (not significant); bencyclan and prenylamine were ineffective; cinnarizine and diltiazem slightly reduced tolerance times as did flunarizine at low doses. At protective doses, verapamil, gallopamil, and nimodipine significantly raised the respiration rate but had little or no cardiac depressor effects. Bencyclan showed ventilatory drive but cardiocirculatory depression. A clear‐cut ventilatory drive did not occur with the other ineffective slow channel inhibitors. It is suggested that the protective actions observed were not due to slow channel inhibition per se, nor to spasmolytic potency or increased cerebral blood flow. Ventilatory drive associated with other cardiopulmonary actions which secondarily raise the brain oxygen supply are likely to be responsible for this effect.