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I Gabauer

Publications and source records attributed to I Gabauer.

69 records · Page 4Linked to original sources
PubMedDate not supplied

Protective effect of calmodulin inhibitors on reperfusion injury.

Activation of an intracellular calcium-calmodulin complex may play an important role in myocardial injury induced by ischemia and reperfusion. Chlorpromazine and trifluoperazine, calmodulin inhibitors, were used to enhance myocardial preservation by preventing harmful effect of intracellular calcium accumulation. The experimental model used one-hour LAD coronary occlusion and subsequent two-hour reperfusion in 70 dogs divided into four groups. Reperfusion alone significantly increased regional myocardial blood flow and left ventricular enddiastolic pressure and significantly reduced infarct size, dp/dt max, V max, mean aortic pressure, cardiac index and index of left ventricular minute work. Phenothiazines, applied at the 30th minute of occlusion significantly reduced infarct size, left ventricular enddiastolic pressure and index of systemic resistance and significantly increased dp/dt max, V max, cardiac index and regional myocardial blood flow in ischemic and border zones. The physiological results tightly correlated with the biochemical results and ultrastructural findings. The present study suggests that phenothiazines can improve cardiac performance and preservation of myocytes by preventing calcium stimulatory effect on degradative enzymes and may represent a potential clinical tool in modifying myocardial injury induced by ischemia and reperfusion.

Animals↗
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On the absorption of drugs using chronic dog ileal loop method.

The absorption rate of three model drugs, i.e., pentacaine (highly lipophilic), stobadine (moderately lipophilic) and acetylsalicylic acid (hydrophilic), was studied using the chronic dog ileal loop method. The drugs were dissolved either in 0.9% unbuffered solution of NaCl or in antacid mixture. When using 0.9% NaCl, the half-lives of absorption (t1/2 (dis)) of pentacaine and stobadine were (mean +/- SD) 23.2 +/- 7.8 min and 20.8 +/- 7.2 min, respectively. For stobadine a good agreement was found between its t1/2 (dis) from the ileum and its absorption half-life determined from blood concentrations after oral administration to dogs. The absorption of acetylsalicylic acid accounted for only 10-20% of the dose introduced into the loop over 45 min; thus, a reliable value of t1/2 (dis) could not be determined. The administration of unbuffered solution of NaCl into the loop was accompanied by rapid increase of pH from acidic to basic value. The antacid mixture failed to affect the absorption rate of the drugs studied. Sampling from the ileum was limited to 35-55 min due to rapid absorption of water. These results suggest that: 1) measurement of the absorption rate of some drugs, e.g., stobadine, by using the chronic dog ileal loop method may adequately predict their absorption rate after peroral administration to the dog, 2) interactions of antacids with drug absorption in the ileum may not play a significant role because of the strong buffering capacity of the ileum, and 3) rapid absorption of water from the ileum does not allow to reliably determine the value of t1/2 (dis) for slowly absorbed drugs.

Administration, Oral↗
PubMedDate not supplied

Further assessment of the protective effect of calmodulin inhibitors against reperfusion injury after acute coronary occlusion in the dog.

OBJECTIVE: To re-evaluate the suitability of chlorpromazine and trifluoperazine to prevent postischemic reperfusion injury of the myocardium. DESIGN: Acute occlusion (60 mins) and subsequent reperfusion (120 mins) of the left anterior descendent coronary artery with monitoring of hemodynamic, morphological and biochemical variables of the heart. SETTING: Experimental study. ANIMALS: Seventy adult mongrel dogs. INTERVENTIONS: Chlorpromazine (15 mg/kg body weight) or trifluoperazine (2 mg/kg body weight) given intravenously 30 mins after the onset of occlusion. MAIN RESULTS: Reperfusion alone increased the regional bloodflow and left ventricular end-diastolic pressure (P < 0.05 to 0.01), and reduced the size of the occluded area. Reperfusion also decreased the dp/dtmax, Vmax, mean aortic pressure, cardiac index, etc, but failed to improve cardiac ultrastructure and metabolism. Chlorpromazine or trifluoperazine induced a further reduction (P < 0.05 to 0.01) in infarct size, left ventricular end-diastolic pressure and systemic resistance index, and caused an increase in dp/dtmax, Vmax, cardiac index and regional bloodflow in the ischemic and border zones of the left ventricle. Moreover, these drugs preserved, to a certain extent, the metabolism of the myocardium and its ultrastructure. CONCLUSIONS: In spite of their considerable preventive effect, neither chlorpromazine nor trifluoperazine provided a complete prevention of reperfusion injury to the myocardium.

Animals↗