Chronic instrumentation and its lack of effect on the hemodynamics and regional myocardial blood flow of conscious dogs.

Inou, Tetsuji; Tomoike, Hitonobu; Watanabe, Kunihiro; Mizukami, M; Kikuchi, Yutaka; Nakamura, Motoomi

doi:10.1536/ihj.26.259

Cited by 5 publications

(2 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ampicillin (0.5 g twice a day) was given for 4 days beginning on the day before surgery. The dogs recovered completely within 1 week, as deduced from their normal behavior, body temperature, heart rate, and respiration, but the investigations were not commenced earlier than 10 days after surgery to guarantee a stable hemodynamic state [7].…”

Section: Materials and Methods Chronic Instrumentationmentioning

confidence: 99%

Antiischemic effects of tedisamil in conscious dogs

Raberger

Grohs

Fischer

1992

Cardiovasc Drug Ther

View full text Add to dashboard Cite

The antiischemic effects of tedisamil were investigated in chronically instrumented conscious dogs. Heart rate, arterial blood pressure, left ventricular dP/dtma x, left ventricular end-diastolic pressure, and regional myocardial shortening in the ischemic and normal myocardium, assessed by sonomicrometry, were measured. Reversible regional myocardial dysfunction was achieved by graded treadmill exercise in the presence of a critical coronary stenosis, which was produced by partial inflation of a hydraulic occluder. Regional myocardial dysfunction, which was observed before the intravenous drug administration, was almost completely abolished by tedisamil (180 p.g/kg/5min). The antiischemic effect of tedisamil is due to a reduction in heart rate, which leads to a decrease in left ventricular dP/dtm~_, and myocardial oxygen demand in the presence of a prolongation of diastole and thus coronary perfusion time. Clinical evaluation will test the value of this drug for the treatment of stressinduced symptomatic and asymptomatic angina pectoris in humans.Tedisamil is a sinus-node inhibitor with K+-channel blocking activity. Other bradycardic drugs that belong to this group are the specific bradycardic agents alinidine and zatebradine (ULFS 49). In contrast to beta-adrenoceptor antagonists, specific bradycardic agents lead to a reduction in heart rate but do not reduce myocardial contractility. Tedisamil was shown to have no or only a negligible negative inotropic effect [1,2].Heart rate is a major determinant of myocardial oxygen needs [3]. Thus decreases in heart rate lead, on the one hand, to a decrease in myocardial oxygen consumption and, on the other hand, to a marked prolongation of diastolic time. Since coronary blood flow occurs mainly during diastole, a decrease in heart rate, and thus an increase in diastolic time, allows a better blood supply and hence oxygen availability, especially in the subendocardial myocardium.Alinidine and zatebradine, both specific bradycardic agents, were shown to abolish regional myocardial dysfunction in a model of exercise-induced regional myocardial underperfusion [4,5]. We therefore investigated the effects of tedisamil in this model [6], which mimicks the hemodynamic features of exerciseinduced myocardial dysfunction in humans. Materials and Methods Chronic instrumentationThe animals used in this study were handled in accordance with the animal welfare regulations of the University of Vienna. The experimental protocol was approved by the Animal Subjects Committee of this institution and the Ministry of Science.The study was carried out in six mongrel dogs weighing between 25 and 32 kg. The animals were vaccinated with Candivac SHLT (distemper, hepatitis, leptospirosis, rabies) and Candur P (parvovirosis), and were free of parasites. They received Loyal dry food (Tagger & Co., Graz) as standard diet and had free access to water. Prior to instrumentation the dogs were trained to stand quietly and to run on a treadmill (Quinton model 1854). In order to keep the animals accustomed ...

show abstract

Section: Materials and Methods Chronic Instrumentationmentioning

confidence: 99%

Antiischemic effects of tedisamil in conscious dogs

Raberger

Grohs

Fischer

1992

Cardiovasc Drug Ther

View full text Add to dashboard Cite

show abstract

“…Ampicillin was given for four days, 0.5 g twice a day, beginning on the day of surgery. The dogs recovered completely within a couple of days, but the investigations were started only 10 days after surgery to guarantee a stable haemodynamic state (Inou et al, 1985). Subendocardial placement of ultrasonic transducers was confirmed at necropsy.…”

Section: Experimental Modelmentioning

confidence: 99%

The effects of nitroglycerin on regional myocardial contractile dysfunction produced by treadmill exercise or isoprenaline stimulation in dogs

Schneider

Grohs

Krumpl

et al. 1988

British J Pharmacology

View full text Add to dashboard Cite

To compare different methods of cardiac stress testing that are clinically applied in the management of coronary heart disease, 2 groups of dogs each were chronically instrumented and subjected to treadmill exercise or isoprenaline infusion in the presence of coronary stenosis. It was of interest to determine differences in haemodynamic and regional myocardial contractile parameters, the response to antianginal therapy (nitroglycerin 15μgkg−1 15min−1, i.v.), and, in particular, whether this response differed according to the mode of cardiac stimulation, i.e. treadmill exercise or isoprenaline infusion. After stenosis of the circumflex branch of the left coronary artery which affected resting myocardial function only minimally, treadmill exercise or isoprenaline infusion induced transient regional contractile dysfunction. Heart rate, arterial blood pressure, left ventricular end‐diastolic pressure and left ventricular dp/dtmax were registered and myocardial oxygen demand was calculated. Regional contractile performance was assessed by ultrasonic distance measurement in the underperfused and in a normally perfused area. Treadmill exercise led to an increase in systolic arterial and left ventricular end‐diastolic pressure. In contrast, isoprenaline‐induced stimulation led to a decrease in diastolic arterial and left ventricular end‐diastolic pressure. Regional contractile function in the critically underperfused area showed a deterioration during both modes of stress. Nitroglycerin completely abolished stress‐induced contractile dysfunction only in the group where treadmill exercise was employed for stimulation. The inability of nitroglycerin to prevent myocardial dysfunction in the isoprenaline group may be due to exhaustion of the arterial and/or venous vasodilator potency of nitroglycerin in the presence of adrenoceptor vasodilatation induced by isoprenaline. These findings indicate that clinical antianginal drug testing and the evaluation of the course of disease in patients with coronary heart disease may be highly dependent on the test method chosen.

show abstract