The Effect of Calcium Channel Blockers on Acute Hemodilution in Hypoxic Dogs. |
Sang Chul Lee, Il Yong Kwak, Seong Deok Kim, Seung Woon Lim |
1Department of Anesthesiology, School of Medicine, Seoul National University, Seoul, Korea. 2Department of Anesthesiology, School of Medicine, Choongbook National University, Choongju, Korea. |
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Abstract |
Hemodilution, which is usually induced by autotransfusion, cardiopulmonary bypass and replace-ment therapy for blood loss, has some advantages in saving blood, improving blood flow and reducing the work-load of myocardium. But the safety and compensatory mechanism can be jeopardized by multiple factors, such as changes in inspired oxygen fraction (FIO,), cardiovascular diseases and drugs with potent cardiovascular actions, because of the disadvantageous hemodynamic changes and reduction of oxygen carrying capacity during hemodilution. Calcium channel blockers (CCB), which have recently gained a great popularity in treating several cardiovascular diseases, can affect cardiovascular system and compensatory mechanism during hemodilution. Therefore, to evaluate the effect of CCB on acute isovolemic hemodilution under the condition of hypoxia, we observed the parameters of hemodynamics and oxygen transport during acute isovolemic hemodilution after bleeding (20 ml/kg) in 16 experimentally induced hypoxic (FIO 0.15) dogs divided into verapamil and diltiazem treated groups. The results were as follows; 1) Hemodynamics; (a) In verapamil treated group, mean arterial pressure (MAP) was lower during experiment, but after hemodilution, central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP) increased greater than in diltiazem treated group.
Verapamil showed a greater negative inotropic effect. (b) Verapamil brought more vasodilatory effect than diltiazem. A significant increase of pul-monary vascular resistance (PVR) appeared after hypoxia, which meant hypoxic pulmonary vasocon-striction in diltiazem treated group. (c) In both groups, cardiac output (CO) was maintained well but heart rate (HR), MAP and rate pressure product (RPP) were decreased afrter hypoxia, bleeding and hemodilution. CCB reduce the work load of heart and myocardial oxygen consumption, thereby protect the myocardium. This effect was greatest after bleeding. 2) Oxygen transport; (a) Arterial oxygen tension (PaO2) was increased after hypoxia, bleeding and hemodilution in both groups and arterial carbon dioxide tension (PaCO2) was decreased after hemodilution in verapamil treated group. Ventilation-perfusion mismatch was improed in both groups, more prominently in verapamil treated group. (b) Oxygen flux (O2Flux) and oxygen consumption (VO2) were maintained well in both groups but oxygen extraction ratio (O2ER) after hypoxia and bleeding, and arterial and mixed venous oxygen content difference (Ca-vO2) after hypoxia were increased in diltiazem treated group. After hemodilu-tion, O2ER was decreased in both groups and Ca-VO2, was decreased in verapamil treated group.
In diltiazem treated group, pH of arterial blood (pHa) and mixed venous oxygen tension (PvO2) were decreased after hypoxia, and PvO2 were decreased after hypoxia, and , was also decreased after hemodilution. Oxygen deficit was not seen in either group and oxygen utilization was more satisfactory in verapamil treated group. 3) After hemodilution with dextran-40, colloid osmotic pressure (COP) increased and ionized calcium (Ca++) decreased in both groups. The above findings indicated that use of CCB during acute isovolemic hemodilution in hypoxic dogs is safe because CCB showed adequate maintenance of cardiac output without any sign of heart failure or reduction of myocardial work despite a negative inotropic effect and vasodilatory effect hemodynamically, and also revealed improvement of ventiltion-perfusion mismatch and smooth maintenance of oxygen transport. Both of the effects were more prominent with verapamil than diltiazem in an equimolar dose. |
Key Words:
Calcium channel blockers; Hypoxic dogs; Acute isovolemic hemodilution; Hemodyna- mics; Oxygen transport |
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