Effects of Milrinone on Hemodynamics and Regional Blood Flow in the Hypoxic Dog

Abstract

ABSTRACT. Milrinone, a therapeutic agent for acute congestive heart failure, has both inotropic and vasodilatory effects, but investigations of these effects of milrinone were almost all conducted under normoxia, and few reports have investigated how milrinone affects the hemodynamics and redistribution of regional blood flow under severe hypoxia. By using colored microspheres, we investigated how milrinone affects hemodynamics and the redistribution of regional blood flow under severe hypoxia. Twelve healthy mongrel dogs were divided into 2 groups. The milrinone group was infused with milrinone cumulatively at 25, 75 and 250 µg/kg for 5 min each. The intact group was infused with saline instead of milrinone. We measured the hemodynamics and cerebrum, cerebellum and kidney blood flow in both groups. Both groups were inspired with 10% oxygen. Milrinone induced significant decrease in mean pulmonary artery and pulmonary vascular resistance, compared with the intact group. In both groups slight decreases in mean arterial pressure, systemic vascular resistance and double-product were seen. In regional blood flow, milrinone-induced increases in blood flow were seen in the cerebrum, cerebellum, and especially in the kidneys. Milrinone's vasodilatory effects were sufficient even under hypoxia. And milrinone increased regional blood flow slightly in the cerebrum and cerebellum, and significantly in the kidneys. These results suggested that milrinone protects against hypoxia-induced organ damage especially in the kidneys. In addition, milrinone is very potent in improving severe congested hemodynamics which complicates hypoxic pulmonary vasoconstriction. KEY WORDS: canine, colored microsphere, hypoxia, milrinone, regional blood flow.

Effects of Olprinone on Myocardial Ischemia-Reperfusion Injury in Dogs

“…This phenomenon suggests that PDE III inhibitors may attenuate myocardial damage after myocardial ischemia-reperfusion injury in dogs. In our previous study, increment of myocardial flow was recognized by olprinone infusion [8]. From these results, we speculate that the phenomenon which was seen in the present study may be due to increment of collateral flow by olprinon's vasodilatory effect during myocardial ischemia.…”

“…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.…”

Antihypertensive effect of total flavone extracts from Puerariae Radix

“…ECG was recorded in standard II mode. The chest was opened in the left fourth intercostal space, the pericardium was cut and a Doppler flowmeter (CBI, USA) was positioned around the aorta for cardiac output (CO) measurement (Setoyama et al, 2002). Blood pressure (BP), left ventricular pressure (LVP) and left ventricular dP/dt max were measured via catheters inserted into the right femoral artery and the left ventricle (from the left carotid artery), respectively.…”

Apart from the Other Members of PDE Inhibitors' Family, Enoximone Does Not Enhance Renal Ischemic Reperfusion Injury: The Effects of Enoximone on Renal Ischemia Reperfusion

“…[5] Setoyama et al pointed out that milrinone (the other member of type III PDE inhibitors) has increased the renal blood flow under hypoxic conditions. [10] In their study on healthy dogs with different inotropic agents, Tobato et al found that the renal blood flow was altered with the use of amrinone and milrinone, though these alterations were not statistically significant. [11] However, all members of the type III PDE inhibitors have similar clinical effects, as the former three drugs, being biypridine derivatives, are chemically diverse from enoximone, an imidazole derivative.…”