Table 6.
Effect of conivaptan on myocardial cells hemodynamics in heart failure animals
| References | Species | Condition of species | Intervention | Results |
|---|---|---|---|---|
| Tahara et al65 | Neonatal rat cardiomyocytes (Wistar rats) | Cultured cells | YM087 (conivaptan) | Dose dependent inhibition of AVP induced protein synthesis |
| Tahara et al66 | Rat vascular smooth muscle cells | Cultured cells | YM087 (conivaptan) | Prevented AVP-induced hyperplasia and hypertrophy of these cells in concentration dependent manner |
| Yatsu et al67 | Dogs (n = 8) (male and female Beagle) | Pacing-induced HF Anesthetized |
Vehicle or 0.1 mg/kg iv conivaptan | Increased cardiac output and stroke volume, reduced LVEDP and TPR, increased urine flow and decreased urine osmolarity |
| Yatsu et al68 | Dogs (n = 11) (male and female mongrel dogs) | Normal Anesthetized |
AVP infusion followed by iv bolus of 0.9% saline followed by 0.1 mg/kg iv conivaptan | Rapidly attenuated the AVP induced decrease in CO and reversed the AVP induced elevation in both LVEDP and TPR |
| Wada et al69 | Rats | MI-induced HF (n = 30) Conscious vs Sham operated control rats Conscious | Aquaretic effect: (n = 30) Vehicle or 0.03, 0.1, 0.3 mg/kg iv conivaptan Or 0.3 mg/kg V2R antagonist SR121463A Hemodynamic effect: (n = 39) Vehicle or 0.1, 0.3 mg/kg iv conivaptan Or 0.3 mg/kg V2R antagonist SR121463A |
Dose dependent increase in urine volume and reduction of urine osmolality in both HF and sham-operated rats. SR121463A had similar effects to conivaptan Reduction of RV systolic and RA pressures, LVEDP, lung and body weight. Increased dP/dtmax/LVP SR121463A caused similar effects except it did not improve dP/dtmax/LVP |
| Wada et al70 | Rats (n = 19) (male Wistar) | MI-induced HF vs Sham operated control rats Conscious |
Aquaretic effect: Vehicle or 0.3 to 3 mg/kg oral conivaptan Hemodynamic effect: Vehicle or 3 mg/kg oral conivaptan |
Higher AVP level in HF compared to sham operated rats Reduction of LVEDP, lung and RV weights and reduced mean blood pressure. No effect on heart rate or LV systolic pressure Conivaptan also increased urine volume and reduced urine osmolarity |
Abbreviations: AVP, arginine vasopressin peptide; CO, cardiac output; HF, heart failure; iv, intravenous; LV, left ventricle; LVP, left ventricular pressure; LVEDP, left ventricle end diastolic pressure; MI, myocardial infarction; RA, right atrium; RV , right ventricle; TPR, total peripheral resistance.