Cardiovascular effects of meloxicam

Non steroidal anti-inflammatory drugs are among the most commonly used drugs all over the world in treatment of a variety of rheumatic disorders and are commonly used in patients with cardio-vascular disorders. The present work, aimed to study the cardiovascular modulatory effects of meloxicam [selective COX-2 inhibitor] through in vitro experiments [isolated rabbits heart and aortic strip] and in vivo study that was done on albino rats, through which we investigated the effect of meloxicam on the blood pressure, by blood pressure transducer, and blood flow to different vascular beds and hence different organs as gastrointestinal tract and kidney, using doppler flowmetry. This work was also accompanied by biochemical studies [Liver and kidney functions]. The results revealed a cardio-stimulatory effect of meloxicam in a dose ranging from 0.03-0.3 micro mol/ml on the heart in vitro, but no change in aortic basal tone. Also, interaction of meloxicam, in dose ranging from 0.03-0.3 micro mol/ml, with different vasopressor agonists [noradrenaline, angiotensin and serotonin] showed no change in aortic basal tone. There was a statistically significant dose dependant increase in the blood pressure upon acute intravenous injection of meloxicam in a dose ranging from 0.03-0.3 micro gram/kg, while chronic intra-peritoneal administration produced no significant changes. Acute intravenous injection of meloxicam in a dose ranging from 0.03 - 0.3 micro g/kg produced an increase in both renal blood flow to the values of 14 +/- 1.3, 17 +/- 3.0 and 21 +/- 2.0 cm/sec and mesenteric blood flow giving values of 21 +/- 2.0, 25 +/- 1.5 and 30.0 +/- 3.0 cm/sec. while chronic administration produced no significant changes. There was no effect of meloxicam on the hindquarter or carotid blood flow in neither acute nor chronic administration. The results of the biochemical studies showed no alteration of the biochemical parameters within therapeutic doses. In conclusion, meloxicam was found to have a positive inotropic effect on the heart and safe towards the kidney and gastrointestinal system, increasing the blood flow to these beds

Antiarrhythmic potency of labetalol HCl in comparison with phentolamine mesylate

Labetalol HCI is a drug which competitively antagonizes both beta and alpha adronoceptors. The present work dealt mainly with the following comparative studies: Antiarrhythmic potency of labetalol HCI against experimentally induced ventricular fibrillation in comparison with phentolamine mesylate. Alpha-adrenoceptor blocking activity of labetalol HCI in comparison with phentolamine mesylate. Regarding the antiarrhythmic potency of labetalol HCI and phentolamine mesylate against experimentally induced ventricular fibrillation revealed clearly that phentolamine mesylate is more potent than labetalol HCI about 6 times. Similarly the comparative study of alpha-adrenoceptor activity of labetalol HCl and phentolamine mesylate denoted clearly that the antagonistic effect of phentolamine mesylate to the alpha-adrenergic receptors was more potent and of more prolonged duration than that to labetalol HCI

Infarct size reduction by timolol and prenylamine

The ability of the B-receptor blocker, timolol and the Ca[2+] channel antagonist prenylamine to limit infarct size [I.S.] was assessed in cats, 5 hours after ligation of the left anterior descending coronary artery [LAD]. In control untreated cats, the S-T segment was raised significantly 30 min. after ligation to reach a value of 0.7 +/- 0.09 MV and was maintained significantly elevated [0.67 +/- 0.07 MV] to the end of the experiment. Ventricular dysrhythmia occurred in 3 out of 6 cats and ended in one of them by ventricular fibrillation and death. Serum CPK level increased significantly from a pre-occlusion level of 94 +/- 5 U/L to reach 724 +/- 60, 5 hours later. The I.S., measured by planimetry in serial cardiac sections, stained by triphenyl tetrazolium stain, was found to measure 315 +/- 34 mm[2] representing 31.67% of the heart. Timolol, given in a dose of 25 ug/kg i.v., 15 min. before ligation of LAD, induced hypotension, sinus bradycardia and decreased S-T segment elevation significantly to 0.13 +/- 0.04 MV. It prevented ventricular dysrhythmia and fibrillation. Timolol also reduced significantly serum CPK level to 195 +/- 17 U/L and I.S. to 9.18%. I.V. administration of prenylamine in a dose of 3 mg/kg was accompanied by sinus bradycardia, and hypotension. The S-T segment was significantly lowered [0.15 +/- 0.04 MV] and ventricular fibrillation was prevented. Both serum CPK level [193 =/- 25 U/L] and I.S. [12.93] were significantly reduced when compared with the corresponding levels in coronary ligated untreated cats. It is concluded that, both timolol and prenylamine could protect the heart against extension of infarct size and its complication. An effect which might be due to decrease in free cytosolic Ca[2+] or through their haemodynamic effects which reduce the cardiac work

Cardioprotective effect of captopril on the catecholamine-induced myocardial necrosis

The cardioprotective effect of captopril, a converting enzyme inhibitor, was studied on the isoprenaline-induced myocardial necrosis [M.N.] in rats. The degree of protection was assessed biochemically by measuring variations in level of serum CPK and histopathologically by estimating infarct size [I.S.]% i.e. surface area of injured myocardium to area of heart sections, after being stained with haematoxylin basic fuchcin picric acid stain. Also, injury currents in ECG were looked for. Pretreatment with captopril in a dose of 100 ug/kg i.p., 15 min. before injection of a necrotizing dose of isoprenaline [300 mg/kg] s.c., was found to be highly protective. The serum CPK and I.S. of rats pretreated with captopril were markedly decreased. Moreover, the injury currents, which were observed in ECG of rats treated with isoprenaline, disappeared in captopril treated rats. Injected 15 min. after isoprenaline, captopril was found to be protective but less effective than if it was administered before isoprenaline although used in the same dose level. The mean values of serum CPK and I.S. of post-treated rats were significantly lower than the corresponding values in isoprenaline-treated rats. Further reduction of the cardioprotective effect of captopril was noticed on increasing the post-treatment interval to 30 min. Captopril protects the heart effectively against catecholamine-induced myocardial necrosis. This protective effect proved to be time-related, the earlier the intervention, the better the results

comparison of the effects of atropine and glycopyrrolate on intact animal and various isolated preparations

Gradually increasing doses of glycopyrrolate and atropine were used separately to abolish the effect of ACH on the carotid arterial blood pressure of anesthetized cat, the force of contraction of isolated mammalian heat, the isolated rabbit's atrial contractions, the isolated rabbit's atrial contractions, the isolated rabbit's intestine and the guinea pig's ileum. All the experiments were repeated using neostigmine instead of acetylcholine. The results the effective anticholinergic properties of both drugs, but marked quantitative discrepancies were found regarding their pharmacological actions. It was observed that the effective dose of glycopyrrolate that bloked the atrial bradycardia of ACh was larger than that of atropine. Clinically, it was found that smaller doses of glycopyrrolate compared to atropine were effective as antisialagogue. Therefore, it would be expected that tachycardia would be much more marked with atropine than with glycopyrrolate in the doses used clinically. It was concluded that glycopyrrolate was safer on the C.V. S. and should be preferred to atropine as an anticholinergic premedication especially in cardiac patients