Development of neurogenic pulmonary edema at different grades of intracranial pressure in cats.

Development of neurogenic pulmonary edema (NPE) subsequent to increased intracranial pressure (ICP) was evaluated in an experimental model in cats. Experiments were conducted in chloralose anaesthetised animals, either on spontaneous respiration or on intermittent positive pressure ventilation. Hemodynamic parameters i.e., mean arterial pressure (MAP) and heart rate (HR) were continuously monitored. Pulmonary artery/right ventricular systolic pressure was recorded in cats on spontaneous respiration. Increase in ICP for 180 minutes caused an increase in extravascular lung water (EVLW) content in both spontaneously breathing and artificially ventilated animals. In spontaneously breathing animals EVLW to blood free dry weight ratio (EVLW/BFDW) was 3.95 +/- 0.16 and 4.96 +/- 0.16 at ICP 40 and 80 mm Hg respectively while in animals on artificial ventilation, at 40, 60, 80 and 100 mm Hg ICP, it was 3.88 +/- 0.11, 4.09 +/- 0.10, 4.50 +/- 0.13 and 5.03 +/- 0.17 respectively. These values were significantly greater (P < 0.05) as compared to that in sham operated animals (3.43 +/- 0.10). This was accompanied by rise in MAP, HR and pulmonary artery pressure. The study establishes the graded development of NPE, the severity of which is proportional to the levels of ICP.

Modulation of morphine induced antinociception by intracerebroventricularly administered captopril.

Captopril when administered intracerebroventricularly (icv) in doses of 100, 300, 500 and 1000 micrograms induced a dose dependent antinociceptive effect in rats. Naloxone pretreatment (10 mg/kg, ip) completely antagonised antinociceptive effect of captopril, suggesting thereby the involvement of brain enkephalinergic system. Captopril 300 micrograms, icv potentiated the antinociceptive effect of morphine in intact animals. The bilateral adrenalectomy did not have any effect on this potentiation as against the reported blockade of potentiation in adrenalectomized animals when captopril was administered by systemic route. Thus potentiation of morphine induced antinociception by icv captopril is unlikely to be exerted through an effect on adrenal function and is most likely due to increased brain enkephalin levels.

Effect of intracerebroventricular administration of angiotensin II on emetic reflex in dogs.

Area postrema is rich in angiotensin II receptors and intravenous (iv) administration of angiotensin II has been reported to elicit emesis. However, in the present study intracerebroventricular (icv) administration of angiotensin II up to a dose of 10 micrograms failed to elicit emesis. It is suggested that presence of a cerebrospinal fluid-brain barrier in area postrema most probably prevents access of icv angiotensin II to its receptors which are otherwise accessible on iv administration.

Role of endogenous opioids and histamine in morphine induced emesis.

The role of opioid and histaminergic system in morphine induced emesis was investigated in dogs. Morphine (25 micrograms, icv) consistently evoked emesis with an average latency of 195 +/- 29 sec which was fully accounted for by an action on the chemoreceptor trigger zone (CTZ) as its ablation rendered animals refractory to vomiting. Intraventricular pretreatment with opioid antagonist naloxone, histamine H1 antagonist mepyramine and H2 antagonists metiamide and cimetidine afforded protection to icv morphine emesis. The CSF histamine concentration was significantly raised 5 min after icv morphine administration. The results suggest that both endogenous opioid and histamine are involved in morphine emesis. Naloxone in high doses (1600 micrograms, icv) elicited emesis which was not blocked by CTZ ablation confirming our earlier report.