Effects of Olprinone on Myocardial Ischemia-Reperfusion Injury in Dogs

Abstract

ABSTRACT. We investigated the effect of olprinone on canine myocardial pump function and myocardial damage after ischemia-reperfusion injury. Three dogs of the experimental group were given olprinone (Olprinone group) and another 3 dogs were served as control (Intact group). All animals were occluded left anterior descending artery for 60 min, followed by 6 hr of reperfusion. In the experiment, hemodynamics, infarct area, creatine kinase and troponin-I were measured. Olprinone infusion induced significantly high cardiac output value and significantly low values in left ventricular end diastolic pressure and systemic vascular resistance index after reperfusion. Also, olprinone tend to attenuate the infarct area, creatine kinase and troponin-I. KEY WORDS: canine, ischemia-reperfusion injury, olprinone.J. Vet. Med. Sci. 68(8): 865-868, 2006 In the field of veterinary clinics, cardiovascular surgery using cardiopulmonary bypass has become one of the promising treatments in recent years. However, open heart surgery sometimes induces myocardial ischemia-reperfusion injury and leads to myocardial dysfunction as well as myocardial infarction [4]. To prevent myocardial dysfunction, various agents such as Na + /H + -exchange inhibitor, oxygenderived free radical scavenger and statins have been studied [10].Phosphodiesterase (PDE) III inhibitors, a therapeutic agent for acute congestive heart failure, have both inotropic and vasodilatory effects. The pharmacological effect of PDE III inhibitors have been shown to be due to an increase in intracellular cyclic-adenosine monophosphate (cAMP) without beta-adrenergic pathway [1-3, 6, 7, 11]. Recently, it has been demonstrated that amrinone and milrinone decreased infarct size in isolated rabbit heart with coronary artery occlusion [12]. Rechtman et al. also reported that amrinone suppressed creatine kinase and lactate dehydrogenase elevation, indicators of myocardial injury, in the isolated rat heart with ischemia-reperfusion injury [9]. In addition, our previous study showed milrinone increases myocardial blood flow in the hypoxic dogs [8]. From these results, we hypothesized that PDE III inhibitors may protect myocardial damage from ischemic or ischemia-reperfusion injury and it seems to have an interesting effect on treating myocardial dysfunction after cardiopulmonary bypass or myocardial infarction.However, few reports have evaluated the effect of PDE III inhibitors on canine myocardial pump function after ischemia-reperfusion injury. In this study, we investigated the effect of olprinone on canine myocardial function and damage after ischemia-reperfusion injury.The experiment was carried out after permission from the committee on Animal Experimentation, Kagoshima University.We used 6 beagle dogs (2 years old, male) weighing 9.2 ± 0.5 kg (mean ± standard error). The dogs were healthy, as determined by pre-operative examinations, including physical examination, clinical laboratory evaluation and radiography of the thorax.The dogs were premedicated with atropin sulfate (0...

Pharmacological preconditioning by milrinone: Memory preserving and neuroprotective effect in ischemia-reperfusion injury in mice

“…Milrinone or olprinone, when administered before ischemia-reperfusion, was cardioprotective and reduced infarct size in dogs (Setoyama et al, 2006). Amrinone and milrinone decrease infarct size in rabbit hearts with coronary artery branch occlusion via vasodilation to increase myocardial perfusion in the tissue surrounding the ischemic zone (Rump et al, 1994).…”

Correlation of Serum Cardiac Troponin I and Myocardial Damage in Cattle with Monensin Toxicosis

“…Studies in laboratory animals 15 and dogs 16 have reported on the diagnostic use of cTnI and concluded that cTnI is both sensitive and specific for the diagnosis of acute myocardial injury. The results of this study confirm such findings.…”

“…Flunixin-meglumine f (1.1 mg/kg, IV) was given for pyrexia and alleviation of gastrointestinal pain as needed. Blood was collected from the indwelling jugular catheter at 4,6,8,12,16,20,24,36,48,72, and 80 hours (Group A) and at 12, 24, 36, 48, 72, 96, 120, and 144 hours (Group B) after monensin administration for serum biochemical analyses and cTnI measurement. The blood was divided equally and put into tubes without anticoagulant.…”

Anti‐ischemic effects of inotropic agents in experimental right ventricular infarction

“…The efficacy of PDE‐III inhibitors has been demonstrated in isolated heart preparations 5,17,18 . However, only two in vivo studies have demonstrated pre‐conditioning effects in dogs 19,20 . These findings might be related to increased collateral flow.…”