Comparison of the effect of the ATP-sensitive potassium channel opener YM934 with that of nitroglycerin on impaired coronary circulation in dogs.

We compared the effect of an ATP-sensitive potassium channel opener, YM934, with that of nitroglycerin (NTG) on impaired coronary circulation in dogs. Coronary stenosis was produced in 7 dogs by placing a hydraulic occluder around the proximal left circumflex coronary (LCx) artery and abolishing reactive hyperemia to compromise the LCx flow. The following parameters were measured: the aortic pressure, LCx flow velocity, LCx vessel diameter, LCx peripheral pressure, and segment length in the LCx area. Subsequently, we occluded the LCx artery for 15 seconds and measured the recovery-interval (time required for the segment shortening to return to the preocclusion value). The measurements were recorded under three study conditions: (1) at baseline without LCx stenosis; (2) with LCx stenosis under NTG infusion (3 microg/Kg/min); and (3) with LCx stenosis after intravenous administration of YM934 (0.3 microg/kg). The heart rate and aortic pressure were similar under the three study conditions. Mean LCx flow velocity and segment shortening did not significantly change either. However, LCx peripheral pressure decreased after the induction of stenosis (P < 0.05) and showed no response to either NTG or YM934. YM934 administration significantly increased LCx flow in the presence of LCx stenosis, (P < 0.05), whereas NTG infusion did not. YM934 significantly shortened the recovery-interval of the segment shortening after 15-sec LCx occlusion (P < 0.05), whereas NTG did not. These findings suggest that YM934 improves coronary blood flow and prevents myocardial ischemic damage in severely impaired coronary circulation.

Randomized comparison of cilostazol vs ticlopidine for antiplatelet therapy after coronary stenting.

BACKGROUND: Cilostazol and ticlopidine are commonly prescribed for prevention of thrombosis after coronary stenting, but few studies have compared them. METHODS AND RESULTS: In the present study 642 patients who underwent stenting were randomized to treatment either with cilostazol + aspirin (C group, 321 patients) or ticlopidine + aspirin (T group, 321 patients). Quantitative coronary angiography (QCA) was performed immediately after stenting and at the 6-month follow-up. Treatment was continued until follow-up angiography. Baseline patient characteristics did not differ significantly. With the exception of a higher rate of stenting in a venous graft in the C group, there were no differences in angiographic characteristics or stent type. Baseline QCA analysis of the reference diameter, minimal lumen diameter (MLD) showed no significant differences. Follow-up QCA analysis of the MLD showed no significant differences. There were also no differences in restenosis or target lesion revascularization rates, or in the incidence of adverse reactions. However, the rate of subacute thrombosis (SAT) was significantly higher in the C group than in the T group (2% vs 0.3%, p=0.02). CONCLUSION: In the present study there was a similar restenosis rate with cilostazol or ticlopidine, but the rate of SAT was significantly higher with cilostazol. There was no significant difference in adverse reactions.

A porcine model of ischemic heart failure produced by chronic placement of a tube in a coronary artery.

BACKGROUND AND AIMS: Animal models of heart failure (HF) are useful to clarify the mechanism and to develop therapeutic interventions. To produce an easy ischemic HF model, we induced myocardial infarction (MI) in pigs by placing a tube in the coronary artery. METHODS: Twelve pigs underwent echocardiography and were randomly allocated to the myocardial infarction group (MI group) and the control group. In the MI pigs, a 4.2 F nylon tube was placed via the carotid artery in the left circumflex coronary (LCx) artery to induce MI. Three months thereafter, thoracotomy was performed in the both groups and left ventricular (LV) pressure-volume relation was evaluated. RESULTS: Body weight, LV dimension and function did not differ in the baseline state between the two groups. Three months after the tube placement, LV diameter was larger (47+/-3 vs. 42+/-2 mm) and its fractional shortening was lower in the MI group than the control group. In addition, aortic flow was decreased, LV ejection fraction was decreased (25+/-5 vs. 52+/-6%) and LV diastolic pressure was elevated (14+/-3 vs. 8+/-2 mmHg) in the MI group compared with the control group. The extent of MI was 26+/-5% of the LV in the MI pigs. CONCLUSION: The method of placing a tube in the coronary artery does not need thoracotomy or an additional procedure and enables the production of an ischemic HF model of pigs.

Effects of nicardipine on coronary, vertebral and renal arterial flows in patients with essential hypertension.

We examined the acute effects of a calcium antagonist, nicardipine, on hemodynamics and blood flow in the left anterior descending coronary (LAD), vertebral and renal arteries of essential hypertensive patients who had complained of chest pain and undergone cardiac catheterization. The blood flow velocities of the LAD, vertebral and renal arteries were measured using a Doppler guidewire and the arterial luminal diameters were measured from the arteriograms. The arterial blood flow was calculated by multiplying the blood flow velocity by the obtained vessel diameter. Coronary flow reserve was evaluated by injecting papaverine into the left coronary artery. After the baseline data had been obtained, intravenous infusion of nicardipine was started and the same hemodynamic, blood flow velocity and arterial diameter measurements were repeated. Blood pressure was decreased and cardiac output was increased by nicardipine infusion. There was a correlation between the decrease in systolic blood pressure and the increase in cardiac output (r = 0.71). The blood flow velocity in the LAD, vertebral and renal arteries tended to increase and there was an increase in the arterial luminal diameter. An increase in blood flow and a lowering of vascular resistance were observed for each artery (p < 0.05). During nicardipine infusion, the diastolic blood flow in the LAD artery was improved (p < 0.05); however, the maximal blood flow in the LAD artery induced by papaverine infusion remained unchanged. Therefore, there is evidence that coronary, vertebral and renal blood flows are improved by nicardipine infusion despite the acute blood pressure reduction.