Øyvind Jakobsen

Oxygen Wasting Effect of inotropy—Is There a Need for a New Evaluation? An Experimental Large Animal Study Using Dobutamine and Levosimendan

Background— We addressed the hypothesis that the inotropic drugs dobutamine and levosimendan both induce surplus oxygen consumption (oxygen wasting) relative to their contractile effect in equipotent therapeutic doses, with levosimendan being energetically more efficient. Methods and Results— Postischemically reduced left ventricular function (stunning) was created by repetitive left coronary occlusions in 22 pigs. This contractile dysfunction was reversed by infusion of either levosimendan (24 μg/kg loading and 0.04 μg · kg−1 · min−1 infusion) or an equipotent dose of dobutamine (1.25 μg · kg−1 · min−1). Contractility and cardiac output were normalized by both drug regimens. The energy cost of drug-induced contractility enhancement was assessed by myocardial oxygen consumption related to the mechanical indexes tension-time index, pressure-volume area, and total mechanical energy. ANCOVA did not reveal any increased oxygen cost of contractility for either drug in these doses. However, both dobutamine and levosimendan at supratherapeutic levels (10 μg · kg−1 · min−1 and 48 μg/kg loading with 0.2 μg · kg−1 · min−1 infusion, respectively) induced a highly significant increase in oxygen consumption related to mechanical work, compatible with the established oxygen-wasting effect of inotropy ( P <0.001 for all mechanical indexes with dobutamine; P =0.007 for levosimendan as assessed by pressure-volume area). Conclusion— Therapeutic levels of neither dobutamine nor levosimendan showed inotropic oxygen wasting in this in vivo pig model. Thus, relevant hemodynamic responses can be achieved with an adrenergic inotrope without surplus oxygen consumption. Received March 17, 2009; accepted November 16, 2009.Background—We addressed the hypothesis that the inotropic drugs dobutamine and levosimendan both induce surplus oxygen consumption (oxygen wasting) relative to their contractile effect in equipotent therapeutic doses, with levosimendan being energetically more efficient. Methods and Results—Postischemically reduced left ventricular function (stunning) was created by repetitive left coronary occlusions in 22 pigs. This contractile dysfunction was reversed by infusion of either levosimendan (24 &mgr;g/kg loading and 0.04 &mgr;g·kg−1·min−1 infusion) or an equipotent dose of dobutamine (1.25 &mgr;g·kg−1·min−1). Contractility and cardiac output were normalized by both drug regimens. The energy cost of drug-induced contractility enhancement was assessed by myocardial oxygen consumption related to the mechanical indexes tension-time index, pressure-volume area, and total mechanical energy. ANCOVA did not reveal any increased oxygen cost of contractility for either drug in these doses. However, both dobutamine and levosimendan at supratherapeutic levels (10 &mgr;g·kg−1·min−1 and 48 &mgr;g/kg loading with 0.2 &mgr;g·kg−1·min−1 infusion, respectively) induced a highly significant increase in oxygen consumption related to mechanical work, compatible with the established oxygen-wasting effect of inotropy (P<0.001 for all mechanical indexes with dobutamine; P=0.007 for levosimendan as assessed by pressure-volume area). Conclusion—Therapeutic levels of neither dobutamine nor levosimendan showed inotropic oxygen wasting in this in vivo pig model. Thus, relevant hemodynamic responses can be achieved with an adrenergic inotrope without surplus oxygen consumption.

Adenosine instead of supranormal potassium in cardioplegia: It is safe, efficient, and reduces the incidence of postoperative atrial fibrillation. A randomized clinical trial

OBJECTIVE We aimed to evaluate the efficacy and safety of a cold crystalloid cardioplegic solution with adenosine (1.2 mmol/L) instead of supranormal potassium. METHODS Sixty low-risk patients scheduled for elective coronary artery bypass grafting (CABG) were randomized to receive standard cold crystalloid hyperkalemic cardioplegia (hyperkalemic group) or normokalemic cardioplegia in which supranormal potassium was replaced with 1.2 mmol/L adenosine (adenosine group). End points were postoperative release of troponin T and creatine kinase MB, hemodynamics measured by PiCCO arterial thermodilution catheters, perioperative release of markers of endothelial activation and injury, and clinical course. RESULTS The adenosine group had a significantly shorter time to arrest than did the hyperkalemic group (mean ± standard deviation, 11 ± 5 vs 44 ± 18 seconds; P < .001). Three hearts in the adenosine group were probably not adequately drained and received additional hyperkalemic cardioplegia to maintain satisfactory cardioplegic arrest. There were no differences between groups with respect to perioperative release of markers of endothelial activation or injury and no differences between groups in postoperative release of troponin T or creatine kinase MB. Postoperative hemodynamics including cardiac index were similar between groups. The incidence of postoperative atrial fibrillation was significantly lower in the adenosine group than in the hyperkalemic group (4 vs 15; P = .01). CONCLUSIONS Adenosine instead of hyperkalemia in cold crystalloid cardioplegia is safe, gives more rapid cardiac arrest, and affords similar cardioprotection and maintenance of hemodynamic parameters, together with a marked reduction in the incidence of postoperative atrial fibrillation.

Oxygen-Wasting Effect of InotropyCLINICAL PERSPECTIVE

Background— We addressed the hypothesis that the inotropic drugs dobutamine and levosimendan both induce surplus oxygen consumption (oxygen wasting) relative to their contractile effect in equipotent therapeutic doses, with levosimendan being energetically more efficient. Methods and Results— Postischemically reduced left ventricular function (stunning) was created by repetitive left coronary occlusions in 22 pigs. This contractile dysfunction was reversed by infusion of either levosimendan (24 μg/kg loading and 0.04 μg · kg−1 · min−1 infusion) or an equipotent dose of dobutamine (1.25 μg · kg−1 · min−1). Contractility and cardiac output were normalized by both drug regimens. The energy cost of drug-induced contractility enhancement was assessed by myocardial oxygen consumption related to the mechanical indexes tension-time index, pressure-volume area, and total mechanical energy. ANCOVA did not reveal any increased oxygen cost of contractility for either drug in these doses. However, both dobutamine and levosimendan at supratherapeutic levels (10 μg · kg−1 · min−1 and 48 μg/kg loading with 0.2 μg · kg−1 · min−1 infusion, respectively) induced a highly significant increase in oxygen consumption related to mechanical work, compatible with the established oxygen-wasting effect of inotropy ( P <0.001 for all mechanical indexes with dobutamine; P =0.007 for levosimendan as assessed by pressure-volume area). Conclusion— Therapeutic levels of neither dobutamine nor levosimendan showed inotropic oxygen wasting in this in vivo pig model. Thus, relevant hemodynamic responses can be achieved with an adrenergic inotrope without surplus oxygen consumption. Received March 17, 2009; accepted November 16, 2009.Background—We addressed the hypothesis that the inotropic drugs dobutamine and levosimendan both induce surplus oxygen consumption (oxygen wasting) relative to their contractile effect in equipotent therapeutic doses, with levosimendan being energetically more efficient. Methods and Results—Postischemically reduced left ventricular function (stunning) was created by repetitive left coronary occlusions in 22 pigs. This contractile dysfunction was reversed by infusion of either levosimendan (24 &mgr;g/kg loading and 0.04 &mgr;g·kg−1·min−1 infusion) or an equipotent dose of dobutamine (1.25 &mgr;g·kg−1·min−1). Contractility and cardiac output were normalized by both drug regimens. The energy cost of drug-induced contractility enhancement was assessed by myocardial oxygen consumption related to the mechanical indexes tension-time index, pressure-volume area, and total mechanical energy. ANCOVA did not reveal any increased oxygen cost of contractility for either drug in these doses. However, both dobutamine and levosimendan at supratherapeutic levels (10 &mgr;g·kg−1·min−1 and 48 &mgr;g/kg loading with 0.2 &mgr;g·kg−1·min−1 infusion, respectively) induced a highly significant increase in oxygen consumption related to mechanical work, compatible with the established oxygen-wasting effect of inotropy (P<0.001 for all mechanical indexes with dobutamine; P=0.007 for levosimendan as assessed by pressure-volume area). Conclusion—Therapeutic levels of neither dobutamine nor levosimendan showed inotropic oxygen wasting in this in vivo pig model. Thus, relevant hemodynamic responses can be achieved with an adrenergic inotrope without surplus oxygen consumption.

Adenosine protects against hypoxic injury at hypothermia in guinea pig papillary muscles

Abstract Objectives. To investigate the protective effects of adenosine against hypoxic injury at hypothermia; both magnitude and mechanisms. Design. Receptor versus non-receptor dependent mechanisms in cardioprotection by adenosine were examined in guinea pig papillary muscles exposed to glucose free hypoxia at 24°C. Contractile force amplitude (CFA) and action potential duration (APD) during increasing concentrations of adenosine at 37°C, 30°C and 24°C normoxia were also examined. Results. CFA was significantly improved after adenosine treatment during hypothermic hypoxia compared to control (80.7±17.4% vs 40.5±10.7%, p<0.001). Adenosine receptor antagonist SPT did not antagonize (64.6±21.1%), and adenosine receptor agonists (APNEA+NECA) could not mimic the cardioprotection (53.8±9.3%). MitoKCa blocker paxilline antagonized the cardioprotection (40.0±7.7%). During normoxic conditions hypothermia-induced increase in CFA was significantly decreased by adenosine (0.12–12 mM) whereas the increase in action potential duration was potentiated. Conclusion. Adenosine (1.2 mM) had marked cardioprotective effect in hypothermic substrate free hypoxia. Possible mechanisms are non-receptor dependent and related to mitoKCa channels. The cardiodepressive effect at hypothermia may contribute to cardioplegia.

Dissection of the right pulmonary artery after blunt trauma

A 46-year old female patient was admitted after a 5-m height fall. Contrast-enhanced CT scan discovered dissection of the right pulmonary artery (Figs 1 and 2) as well as rib fractures, pneumo-/ haemothorax, pulmonary contusions and pneumomedistinum. The dissection was confirmed by another CT scan 6 days later. The course was nonoperatively and uneventful. Figure 1: CT scan revealed dissection of the right pulmonary artery. The patient had no past medical history and particularly no chronic pulmonary hypertension due to congenital cardiac anomaly which is the main cause of spontaneous pulmonary artery dissection. Pulmonary artery dissection after blunt trauma has been scarcely described previously.

Oxygen-Wasting Effect of InotropyCLINICAL PERSPECTIVE: Is There a Need for a New Evaluation? An Experimental Large-Animal Study Using Dobutamine and Levosimendan

Background— We addressed the hypothesis that the inotropic drugs dobutamine and levosimendan both induce surplus oxygen consumption (oxygen wasting) relative to their contractile effect in equipotent therapeutic doses, with levosimendan being energetically more efficient. Methods and Results— Postischemically reduced left ventricular function (stunning) was created by repetitive left coronary occlusions in 22 pigs. This contractile dysfunction was reversed by infusion of either levosimendan (24 μg/kg loading and 0.04 μg · kg−1 · min−1 infusion) or an equipotent dose of dobutamine (1.25 μg · kg−1 · min−1). Contractility and cardiac output were normalized by both drug regimens. The energy cost of drug-induced contractility enhancement was assessed by myocardial oxygen consumption related to the mechanical indexes tension-time index, pressure-volume area, and total mechanical energy. ANCOVA did not reveal any increased oxygen cost of contractility for either drug in these doses. However, both dobutamine and levosimendan at supratherapeutic levels (10 μg · kg−1 · min−1 and 48 μg/kg loading with 0.2 μg · kg−1 · min−1 infusion, respectively) induced a highly significant increase in oxygen consumption related to mechanical work, compatible with the established oxygen-wasting effect of inotropy ( P <0.001 for all mechanical indexes with dobutamine; P =0.007 for levosimendan as assessed by pressure-volume area). Conclusion— Therapeutic levels of neither dobutamine nor levosimendan showed inotropic oxygen wasting in this in vivo pig model. Thus, relevant hemodynamic responses can be achieved with an adrenergic inotrope without surplus oxygen consumption. Received March 17, 2009; accepted November 16, 2009.Background—We addressed the hypothesis that the inotropic drugs dobutamine and levosimendan both induce surplus oxygen consumption (oxygen wasting) relative to their contractile effect in equipotent therapeutic doses, with levosimendan being energetically more efficient. Methods and Results—Postischemically reduced left ventricular function (stunning) was created by repetitive left coronary occlusions in 22 pigs. This contractile dysfunction was reversed by infusion of either levosimendan (24 &mgr;g/kg loading and 0.04 &mgr;g·kg−1·min−1 infusion) or an equipotent dose of dobutamine (1.25 &mgr;g·kg−1·min−1). Contractility and cardiac output were normalized by both drug regimens. The energy cost of drug-induced contractility enhancement was assessed by myocardial oxygen consumption related to the mechanical indexes tension-time index, pressure-volume area, and total mechanical energy. ANCOVA did not reveal any increased oxygen cost of contractility for either drug in these doses. However, both dobutamine and levosimendan at supratherapeutic levels (10 &mgr;g·kg−1·min−1 and 48 &mgr;g/kg loading with 0.2 &mgr;g·kg−1·min−1 infusion, respectively) induced a highly significant increase in oxygen consumption related to mechanical work, compatible with the established oxygen-wasting effect of inotropy (P<0.001 for all mechanical indexes with dobutamine; P=0.007 for levosimendan as assessed by pressure-volume area). Conclusion—Therapeutic levels of neither dobutamine nor levosimendan showed inotropic oxygen wasting in this in vivo pig model. Thus, relevant hemodynamic responses can be achieved with an adrenergic inotrope without surplus oxygen consumption.

Oxygen-Wasting Effect of Inotropy

Background— We addressed the hypothesis that the inotropic drugs dobutamine and levosimendan both induce surplus oxygen consumption (oxygen wasting) relative to their contractile effect in equipotent therapeutic doses, with levosimendan being energetically more efficient. Methods and Results— Postischemically reduced left ventricular function (stunning) was created by repetitive left coronary occlusions in 22 pigs. This contractile dysfunction was reversed by infusion of either levosimendan (24 μg/kg loading and 0.04 μg · kg−1 · min−1 infusion) or an equipotent dose of dobutamine (1.25 μg · kg−1 · min−1). Contractility and cardiac output were normalized by both drug regimens. The energy cost of drug-induced contractility enhancement was assessed by myocardial oxygen consumption related to the mechanical indexes tension-time index, pressure-volume area, and total mechanical energy. ANCOVA did not reveal any increased oxygen cost of contractility for either drug in these doses. However, both dobutamine and levosimendan at supratherapeutic levels (10 μg · kg−1 · min−1 and 48 μg/kg loading with 0.2 μg · kg−1 · min−1 infusion, respectively) induced a highly significant increase in oxygen consumption related to mechanical work, compatible with the established oxygen-wasting effect of inotropy ( P <0.001 for all mechanical indexes with dobutamine; P =0.007 for levosimendan as assessed by pressure-volume area). Conclusion— Therapeutic levels of neither dobutamine nor levosimendan showed inotropic oxygen wasting in this in vivo pig model. Thus, relevant hemodynamic responses can be achieved with an adrenergic inotrope without surplus oxygen consumption. Received March 17, 2009; accepted November 16, 2009.Background—We addressed the hypothesis that the inotropic drugs dobutamine and levosimendan both induce surplus oxygen consumption (oxygen wasting) relative to their contractile effect in equipotent therapeutic doses, with levosimendan being energetically more efficient. Methods and Results—Postischemically reduced left ventricular function (stunning) was created by repetitive left coronary occlusions in 22 pigs. This contractile dysfunction was reversed by infusion of either levosimendan (24 &mgr;g/kg loading and 0.04 &mgr;g·kg−1·min−1 infusion) or an equipotent dose of dobutamine (1.25 &mgr;g·kg−1·min−1). Contractility and cardiac output were normalized by both drug regimens. The energy cost of drug-induced contractility enhancement was assessed by myocardial oxygen consumption related to the mechanical indexes tension-time index, pressure-volume area, and total mechanical energy. ANCOVA did not reveal any increased oxygen cost of contractility for either drug in these doses. However, both dobutamine and levosimendan at supratherapeutic levels (10 &mgr;g·kg−1·min−1 and 48 &mgr;g/kg loading with 0.2 &mgr;g·kg−1·min−1 infusion, respectively) induced a highly significant increase in oxygen consumption related to mechanical work, compatible with the established oxygen-wasting effect of inotropy (P<0.001 for all mechanical indexes with dobutamine; P=0.007 for levosimendan as assessed by pressure-volume area). Conclusion—Therapeutic levels of neither dobutamine nor levosimendan showed inotropic oxygen wasting in this in vivo pig model. Thus, relevant hemodynamic responses can be achieved with an adrenergic inotrope without surplus oxygen consumption.