Differential effects of selective and non-selective nitric oxide synthase inhibitors on the blood perfusion of ischemia-reperfused myocardium in dogs.

BACKGROUND: Nitric oxide (NO) is protective for the cardiovascular system, and excessive NO exerts negative effects on the circulatory system. This study aimed to compare the effects of selective or non-selective NO synthase (NOS) inhibitors on blood flow perfusion of ischemia-reperfused myocardium. MATERIAL AND METHODS: Male mongrel dogs were randomly assigned to 4 groups: only ischemia-reperfusion (control), ischemia-reperfusion plus Nù-nitro-L-arginine methyl ester (NAME) treatment, ischemia-reperfusion plus aminoguanidine (AMD) treatment, and sham operation group. Myocardial contrast echocardiography (MCE) was performed. Blood samples were taken for measurement of NO. Background-subtracted peak videointensity (PVI) and PVI ratio in myocardium were measured. RESULTS: In the NAME-treated group, the PVI at 5 min reperfusion did not significantly differ from pre-LAD-occlusion, but declined to and retained at a level obviously lower than the pre-LAD-occlusion. In the AMD-treated group, the PVI at 5 min reperfusion was significantly higher than at pre-LAD-occlusion, and then restored to and remained at the pre-LAD-occlusion level. The changes of PVI ratios in the 3 groups were similar to PVI values. In the AMD-treated group, the curve width increased in the early reperfusion, but returned to the pre-LAD-occlusion level at 90 min reperfusion. The plasma NO concentration in the NAME-treated group greatly decreased and remained low during the whole period of reperfusion. In the AMD-treated group, there were only slight increases in NO concentrations during reperfusion. CONCLUSIONS: NAME totally inhibited NO production and attenuated myocardial blood flow perfusion. Aminoguanidine significantly relieved the increase in NO production and alleviated the congestion of reperfused myocardium. Selective inhibitors of iNOS might be useful in the management of certain diseases associated with ischemia-reperfusion.

Effects of drag-reducing polymers on microcirculation of normal rat hindlimb skeletal muscle / 中国医学科学院学报

<p><b>OBJECTIVE</b>To observe the effects of polyethylene oxide (PEO) on microcirculation of normal rat hindlimb skeletal muscle.</p><p><b>METHODS</b>Sixteen male Wistar rats were anesthetized and equally and randomly divided into PEO group (administered with 10 ppm PEO solution) and control group (administered with equal volume of normal saline). The PEO solution or saline was separately injected through the caudal vein at a constant rate of 5 ml/h for 20 minutes. Using short axis view at right mid thigh region, contrast-enhanced ultrasonography was performed before and after the administration of solution. Electrocardiogram, blood pressure, and central venous pressure were also monitored.</p><p><b>RESULTS</b>In the PEO group, after the administration of PEO, microcirculation capillary volume increased from (20.78±2.63) dB to (22.40±1.94) dB (P=0.023), red blood cell velocity from (0.27±0.08) s-1 to (0.35±0.13) s-1(P=0.010), and capillary blood flow from (5.65±1.81) dB/s to (7.91±3.28) dB/s (P=0.013). In the control group, there were no significant changes in microcirculation capillary volume, red blood cell velocity, and capillary blood flow (all Pþ0.05) after the injection of normal saline. The changes of heart rates, blood pressures and central venous pressure were not significant after the administration of either PEO or saline (all Pþ0.05).</p><p><b>CONCLUSION</b>PEO can remarkably increase capillary volume, red blood cell velocity, and capillary blood flow in normal rat hindlimb skeletal muscle.</p>

Coronary microcirculation changes during myocardial stunning in dogs.

OBJECTIVE: To investigate changes in the coronary microcirculation during myocardial stunning in dogs. METHODS: Male mongrel dogs underwent a 15- or 60-min occlusion of the left anterior descending coronary artery, followed by a 120-min reperfusion. Myocardial contrast echocardiography was performed before and after treatment with acetylcholine (ACH) or nitroglycerin (NG). Peak videointensity (PVI) in the myocardial zone was measured, and myocardial samples were examined using transmission electron microscopy. RESULTS: In the 15-min group, the ratio of the PVI between the stunned and intact myocardial zone (PVIR) before and after treatment with NG (NG-PVIR) or ACH (ACH-PVIR) declined markedly in the early period of reperfusion and then returned to preligation levels. In the 60-min group, NG-PVIR was reduced in the early period of reperfusion and then returned to its preligation level. A low level of ACH-PVIR lasted during the entire 120-min reperfusion. Similar changes in the ratio of the PVIR before and after treatment with NG or ACH were observed. In the 60-min group, capillary endothelial edema and widening of intercellular linking gaps were observed. CONCLUSIONS: We observed microvascular endothelial damage and endothelium-dependent dilatation impairments in stunned myocardium, and their severity and recovery rate are affected by the duration of ischemia.

[Quantitative evaluation of canine renal blood flow with contrast-enhanced ultrasound].

OBJECTIVE: To evaluate the accuracy of contrast-enhanced ultrasound (CEU) in renal blood flow quantification. METHODS: Regional renal perfusion was quantified with CEU in 10 dogs at the baseline level and after treatment with 3 doses of dopamine (3, 8 and 16 mg.kg(-1).min(-1)), and renal arterial flow (RAF) was measured with ultrasonic flow probes deployed directly on the renal artery simultaneously. Normalized RAF was calculated as RAF divided by renal weight (ml.min(-1).g(-1)). RESULTS: Compared with the baseline level, a progressive increase in RAF was induced by dopamine treatment at the doses of 3 and 8 mg.kg(-1).min(-1) (P<0.05), but at a higher dose of 16 mg.kg(-1).min(-1), the increment in RAF was reduced in comparison with that with the two lower doses (P<0.05). The same changes in cortical nutrient blood flow derived from CEU were observed. Significant positive correlation was found between normalized RAF and CEU-derived cortical nutrient blood flow (y=39.8x + 44.3, r=0.88, P<0.001). CONCLUSION: CEU can be used to accurately quantify renal blood flow in dogs.

[Cardioprotective effects of K(ATP) channel opener nicorandil during ischemia/ reperfusion in dogs].

OBJECTIVE: To further confirm the effect of nicorandil in reducing the area of myocardial infarct is through the mediation of activation of the KATP channel but not by its nitrate-like properties, and to determine whether the protective effect is the same or not when the drug is either given immediate after infarction or after reperfusion. METHODS: Thirty-five dogs were randomly divided into five groups as follows. Ischemia/reperfusion (IR) group: the dogs were subjected to 90 minutes of left anterior descending coronary artery(LAD) occlusion followed by 120 minutes reperfusion. Pre-nicorandil (PNIC) group: nicorandil(NIC) 100 microg/kg was administrated by intravenous injection 10 minutes before occlusion, followed by infusion of 10 microg x kg(-1) x min (-1) of the drug till the end of reperfusion. Ischemia nicorandil(INIC) group: NIC 100 microg/kg was administered by intravenous injection 15 minutes after occlusion and 10 microg x kg(-1) x min (-1) of drug intravenously till the end of reperfusion. In the Onset reperfusion treated with nicorandil(RNIC) group: NIC 100 microg/kg was administered intravenously at the onset of reperfusion followed by 10 microg x kg(-1) x min (-1)of drug intravenously up to the end of reperfusion. Glibenclamide(GLIB)+INIC group: before NIC was administered, dogs were pretreated with GLIB 0.3 mg/kg for 10 minutes, and other treatment was the same as INIC group. Hemodynamics data were determined as baseline, 60 minutes post-occlusion, and 120 minutes post-reperfusion. By using 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, the infarct areas were analyzed with image analyzer. RESULTS: The results showed that at 60 minutes post-occlusion, cardiac output (CO) was reduced in every group compared with baseline (all P<0.01), CO value recovered at 120 minutes after reperfusion in both PNIC and INIC group (P>0.05). There were no significant differences in heart rate (HR), mean artery pressure(MAP), mean pulmonary artery pressure(MPAP), pulmonary capillary wedge pressure(PCWP) values among all the groups. A marked reduction in the infarct area was found in PNIC group and INIC group (P<0.01) compared with IR group. Administration of GLIB before INIC shows to have no protective effect (P>0.05). CONCLUSION: Our study shows that nicorandil which is a K ATP channel activator, could mimic the effect of ischemic pre-conditioning of the myocardium, by reducing the area of myocardial infarct.