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Biomedical subjects

R A Tio

Publications and source records attributed to R A Tio.

63 records · Page 4Linked to original sources
PubMed1990

The effects of oral pretreatment with zofenopril, an angiotensin-converting enzyme inhibitor, on early reperfusion and subsequent electrophysiologic stability in the pig.

The effects of oral zofenopril pretreatment were investigated in a chronic closed-chest pig model of ischemia and reperfusion. Pigs (25-35 kg) were pretreated orally with zofenopril (15 mg/day) on the 2 days prior to ischemia, which was evoked by the inflation of a catheter balloon in the left anterior descending coronary artery over 45 minutes. The catheter was then removed and the myocardium was reperfused. After 2 weeks, infarct properties were assessed by signal averaging of the body surface electrocardiogram and the inducibility of malignant ventricular tachyarrhythmias was tested with a programmed electrical stimulation protocol. A significant increase in the pressure-rate product (43 +/- 11%, mean +/- SEM), indicating the oxygen demand of the heart, was prevented by zofenopril (19 +/- 8%, p less than 0.05). Zofenopril reduced the peak efflux of adrenaline (1302 +/- 213 vs. 3201 +/- 760 pg/ml; p less than 0.05), noradrenaline (402 +/- 54 vs. 902 +/- 282 pg/ml; p less than 0.05), and of the adenosine catabolites inosine and hypoxanthine (56 +/- 4 vs. 78 +/- 9, pg/ml; p less than 0.05) in the coronary venous effluent. The efflux of the cytoplasmatic enzyme creatine phosphokinase was not significantly reduced after zofenopril (p = 0.08). No difference in plasma renin levels between the groups were found. After 2 weeks, late potentials were found only in the surviving animals from the untreated group, i.e., the voltage vector magnitude was more reduced, and a prolongation of the QRS duration and of the terminal low-amplitude part of the high-frequency QRS were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Basic pharmacology of ACE-inhibitors with respect to ischaemic heart disease: prostaglandins and bradykinin.

Experimental evidence suggests that ACE-inhibitors possess cardioprotective properties. Since ACE-inhibitors can prevent bradykinin breakdown and can stimulate prostaglandin production, it is thought that these cardioprotective effects are mediated by bradykinin and prostaglandins. This article summarizes the results indicating that bradykinin and prostaglandins, although not the only factors, do play an important role in cardioprotection by ACE-inhibitors. Special attention is paid to the presence of the sulphydryl moiety of certain ACE-inhibitors. Probably, these sulphydryl group-containing ACE-inhibitors have an additional protective effect through an interaction with bradykinin or through scavenging of free radicals. However, these cardioprotective effects have not yet been shown in patients with ischaemic heart disease, although some studies indicate that ACE-inhibitors are also able to cause anti-ischaemic effects in patients. Further studies are required to establish the clinical importance of cardioprotection by ACE-inhibitors in ischaemic heart disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1990

Effects of isradipine on hemodynamic parameters and ventricular tachycardia in healed myocardial infarction.

The calcium-entry blocker isradipine was tested in a closed-chest pig model for chronic myocardial infarction. Ischemia was evoked in anesthetized pigs (25-35 kg) by inflating a catheter balloon in the left anterior descending coronary artery for at least 45 min. Hemodynamic monitoring and signal averaging of X, Y, and Z electrocardiographic leads were performed (150 beats, filtered at 50 Hz). After reperfusion, all animals developed an accelerated idioventricular rhythm and high creatine kinase (CPK) plasma levels. Coronary venous purines and catecholamines increased transiently. Two hours after reperfusion, heart rate was elevated from the initial 87.5 +/- 6.3 to 126 +/- 6.4 beats/min (p less than 0.01) and the pressure-rate product (PRP, an index of oxygen demand) from 9,530 +/- 630 to 11,950 +/- 790 mm Hg/min (p less than 0.05). After 2 weeks, six surviving pigs had a decreased stroke volume (98 +/- 18 versus the initial 124 +/- 14 microliters/kg, p less than 0.05), a prolonged high-frequency signal-averaged QRS duration (81.2 +/- 6.5 versus 65.7 +/- 2.9 ms, initially; p less than 0.05), and ventricular tachycardias (VTs), inducible by programmed electrical stimulation (PES). After the infusion of isradipine (1 microgram/kg/min for 30 min), the cardiac index increased from 92 +/- 14 to 133 +/- 8.7 ml/min.kg (p less than 0.02). Even at a higher heart rate, the PRP dropped from 12,600 +/- 1,900 to 10,560 +/- 1,400 mm Hg/min (p less than 0.05). Sustained monomorphic tachycardias were inducible in five pigs before and in three pigs after isradipine, and no deterioration of the signal-averaged electrocardiogram parameters was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The effects of bradykinin and the ischemic isolated rat heart.

The converting enzyme not only converts angiotensin I into angiotensin II but also metabolizes bradykinin. Furthermore, the effects of ischemia on myocardial tissue damage can be modulated by converting enzyme inhibitors. It is unknown whether these effects of ACE-inhibitors are due to increased bradykinin production. In this paper we describe the effects of captopril on bradykinin production in the ischemic isolated rat heart. The reduced deleterious effects of ischemia by captopril were associated with a stimulated bradykinin production. Beneficial effects of bradykinin could be due to an improved perfusion or to an effect on cellular metabolism. Therefore, we conclude that this effect on kinins by ACE-inhibitors is of importance in modulating tissue damage during ischemia.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

The haemodynamic effects of two angiotensin converting enzyme inhibitors, enalaprilat and zofenoprilat, in the rat: evidence for the involvement of bradykinin.

Since angiotensin converting enzyme (ACE) metabolizes bradykinin, the hypotensive effect of ACE inhibitors could be partly due to an increased bradykinin activity. We therefore investigated the influence of HOE K86-4321 [D-Arg-(Hyp2-Thi5,8-DPhe7)-bradykinin], a selective bradykinin-2 receptor antagonist, on the effects of enalaprilat (0.3 and 3.0 mg/kg) and zofenoprilat (0.1 and 1.0 mg/kg) on the heart rate, mean arterial blood pressure, cardiac output and total peripheral resistance in rats. Both enalaprilat and zofenoprilat reduced mean arterial pressure (from 110 +/- 7 to 85 +/- 6 and from 108 +/- 9 to 72 +/- 9 mmHg, respectively; P less than 0.05) and total peripheral resistance (from 515 +/- 35 to 413 +/- 29 and from 495 +/- 45 to 310 +/- 25 x 10(-3) mmHg/litre per min per kg, respectively; P less than 0.05); the heart rate and cardiac output changed little. In the presence of HOE K86-4321, which by itself did not affect the haemodynamic variables measured, the effects of the two ACE inhibitors were significantly reduced. These results suggest that bradykinin-2 receptor-mediated vasodilation, although not involved in blood pressure regulation, influences the reduction in blood pressure induced by enalaprilat and zofenoprilat in normotensive rats. Furthermore, at comparable ACE-inhibiting doses, zofenoprilat was more effective in reducing mean arterial pressure, which might be related to the presence of a sulphydryl group.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Beneficial effects of bradykinin on porcine ischemic myocardium.

Exogenous bradykinin was administered to pigs in which an experimental infarction was evoked by ischemia and reperfusion. Ischemia (45 min) was induced in a closed-chest model with a balloon catheter in the left anterior descending artery, reperfusion by deflating and removing the balloon. The pigs were treated with saline (n = 11) or bradykinin (0.1 mg/kg in 30 min) infusion (n = 10) during the last 15 min of the ischemic period and the first 15 min of reperfusion. During ischemia, heart rate increased in the saline group to 120 +/- 9% of the initial value (p less than 0.05) and in the bradykinin group to 155 +/- 13% (p less than 0.05). After reperfusion, the rate-pressure product was increased in both groups. The increase of arterial creatine kinase levels was significantly less in the bradykinin-treated group. However, the catecholamine and purine levels were increased, as was the plasma renin activity when compared with the saline group. Two weeks after the infarction, six pigs had died in each group. In three out of five surviving saline-treated pigs and one out of four surviving bradykinin-treated pigs, a sustained ventricular tachyarrhythmia was inducible after programmed electrical stimulation. In conclusion, although systemically administered bradykinin caused a temporary increase in myocardial ischemia, it did reduce the (enzymatic indices of) infarct size. Therefore, the beneficial effects, previously found for ACE-inhibitors might at least partially be related to the potentiation of endogenous bradykinin.

Animals↗
PubMedDate not supplied

Gene therapy to prevent restenosis, the Boston experience.

The delivery of genetic material to the vessel wall is being explored as a means to treat disorders of the vasculature. Gene therapy offers the possibility to directly or indirectly influence the molecular pathways that are disregulated. With regard to postangioplasty restenosis, gene therapy is most often aimed at inhibition of vascular smooth muscle cell (VSMC) proliferation. Here, we review the results of studies in our laboratories that have investigated a number of different strategies to inhibit proliferative vessel wall lesions. These strategies include the administration of genes that block cell cycle progression, induce apoptosis, or promote the growth of vascular endothelium.

Adenoviridae↗
PubMedDate not supplied

Neurohumoral changes and the inducibility of ventricular tachycardias: effect of early reperfusion on the ischemic porcine myocardium.

The effects of early reperfusion were studied in closed-chest pigs subjected to either 45 min or 3 hr of regional ischemia. Myocardial enzyme release during early reperfusion and electrophysiological stability after two weeks were assessed. Coronary artery occlusion durations of 3 hr and early reperfusion after 45 min were compared. The creatine phosphokinase levels in the coronary effluent were lower after early reperfusion (p less than 0.001). Moreover, in the early reperfusion group, the coronary sinus catecholamine and purine levels rose to higher values than in the 3 hr group. The plasma levels of catecholamines and the plasma renin activity increased rapidly but transiently at reperfusion in the 45 min group. Both the rate-pressure product and the heart rate were elevated at the end of the reperfusion period (p less than 0.001) in the 45 min group. Survival for two weeks was 3 out of 6 animals in the 3 hr group and 5 out of 8 in the 45 min group. In all but one surviving animal, sustained ventricular tachycardias were inducible by programmed stimulation. Abnormally low QRS amplitudes and delayed potentials were found in the signal-averaged electrocardiogram in the early reperfusion group only. In conclusion, early reperfusion causes a reduction of myocardial tissue damage, but simultaneously, neurohumoral parameters showed a greater activation of the sympathetic nervous system and the renin-angiotensin system apparently causing a deleterious increase in oxygen consumption. Therefore, this injurious component of early reperfusion might prevent the potentially beneficial effects of a reduced tissue damage on survival or late arrhythmias.

Animals↗