Lambertus J. Drop

Relation between ionized calcium concentration and ventricular pump performance in the dog under hemodynamically controlled conditions

The effect of plasma ionized calcium concentration on left ventricular function was studied in the canine heart on right heart bypass. Stroke volume, mean arterial pressure and heart rate were controlled. Plasma ionized calcium was lowered to 0.58 +/- 0.01 mM by citrate infusion and raised to 1.70 +/- 0.01 mM by calcium chloride infusion in random order in each dog. Left ventricular function at each of these ionized calcium levels was compared with that in an immediately preceding normocalcemic period. At a constant stroke work (16.9 +/- 0.2 g-m), sustained hypercalcemia was associated with a small decrease in left ventricular end-diastolic pressure (1.7 +/- 0.7 cm H2O, p less than 0.05) despite a marked increase in peak left ventricular dP/dt (first derivative of ventricular pressure) averaging 34 percent (p less than 0.001). Coronary blood flow, tension-time index and myocardial oxygen consumption were not significantly altered. Stroke work determined at a left ventricular end-diastolic pressure of 14 cm H2O, by interpolation in left ventricular function curves, was 11 +/- 4.4 percent above that at control normocalcemia (p less than 0.05). At a constant stroke work (16.9 +/- 0.2 g-m), sustained hypocalcemia was associated with a marked depression of left ventricular function as demonstrated by a substantial increase (from 4.9 +/- 0.3 to 12.7 +/- 1.1 cm H2O, p less than 0.0001) in left ventricular end-diastolic pressure (p less than 0.0001), decreased mean systolic ejection rate (p less than 0.01) and decreased peak left ventricular dP/dt (p less than 0.0001). Coronary blood flow increased (p less than 0.05) whereas myocardial oxygen consumption did not change significantly. A marked displacement of left ventricular function curves to the right (compared with curves obtained during normocalcemia) was observed, and stroke work determined at a left ventricular end-diastolic pressure of 14 cm H2O was 52 +/- 5.4 percent below control level (p less than 0.001). It appears that hypercalcemia, when initiated from a normal control level, provides only a small enhancement of ventricular pump performance (as indexed by the stroke work-left ventricular end-diastolic pressure relation) despite a marked increase in peak left ventricular dP/dt, whereas marked improvement of left ventricular performance may be expected when calcium infusion is initiated from an ionized calcium level that is below normal.

Mechanical performance of the working rat heart: Response to calcium

Although calcium is generally considered a substance that can enhance cardiac pump performance, few data exist to demonstrate such effect when plasma ionized calcium is varied in the clinical concentration range. We have studied the relationship between perfusate ionized calcium concentration ([Ca2+]) and myocardial mechanical performance in the isolated, blood perfused, ejecting rat heart. With pre- and afterload near constant, observations were made before and after steadystate increases in [Ca2+] from low (mean ± SEM: 0.74 ± 0.01 mM) to normal (1.01 ± 0.04 mM); from low (1.01 ± 0.02 mM) to higher than normal (1.45 ± 0.04 mM, i.e., within the clinical hypercalcemia range); and to an excessive value (1.94 ± 0.03 mM). When [Ca2+] was increased from low to normal levels, aortic blood flow and stroke volume increased by approximately 25% of control (P < 0.025); heart rate did not change significantly. In contrast, when [Ca2+] was raised from 1.03 mM (normal value) to 1.45 mM (within the clinical hypercalcemia range) or to 1.94 mM (above the clinical hypercalcemia range), the changes in aortic flow and stroke volume were less (P < 0.05) as compared to those observed when ionized calcium was adjusted from a level below normal. We conclude that the isolated, blood-perfused heart with pre- and afterload near constant, responds to sustained increases in perfusate ionized calcium with increased aortic flow and stroke volume, but that these changes are disproportionally small when ionized calcium is elevated to above normal from a normal baseline value.

Myocardial oxygen consumption with isoproterenol versus calcium chloride in hypocalcemic ventricular failure in dogs

In 30 dogs on right heart bypass we compared the effects of isoproterenol with those of calcium chloride on myocardial oxygen consumption and on left ventricular function in the setting of ventricular depression produced by ionized hypocalcemia. In 22 dogs (Groups A and B) either isoproterenol or calcium chloride was infused, left ventricular function curves were generated, and end-diastolic pressure vs segment length plots were obtained. In 8 dogs (Group C), with initial hypocalcemia, both isoproterenol and calcium chloride were infused separately in random order to produce an equal decrease in left ventricular end-diastolic pressure at constant mean aortic pressure, heart rate, and cardiac output. Myocardial oxygen consumption and indices of left ventricular function were obtained. In Groups A and B, both drugs, when administered to the ventricle depressed by hypocalcemia, displaced left ventricular function curves upward and to the left. Left ventricular stroke work at constant left ventricular end-diastolic pressure increased (from 13.0 +/- 1.3 to 31.2 +/- 2.3 g X m for isoproterenol; from 13.9 +/- 2.5 to 32.5 +/- 2.5 g X m for calcium chloride). In Group C, there were no significant differences between left ventricular end-diastolic pressure, end-diastolic internal diameter, myocardial oxygen consumption, or peak left ventricular dP/dt in the hypocalcemic periods preceding isoproterenol and calcium chloride infusion. When the two drugs caused matched decreases in left ventricular end-diastolic pressure (-7.4 +/- 0.5 cm H2O for isoproterenol; -7.3 +/- 0.8 cm H2O for calcium chloride) there were similar decreases in end-diastolic internal diameter. However, isoproterenol was associated with a significantly greater (P less than 0.001) myocardial oxygen consumption (13.7 +/- 0.4 ml X 100 g-1 X min-1) than calcium chloride infusion (11.9 +/- 0.4 ml X 100 g-1 X min-1), as well as a greater peak left ventricular dP/dt (P less than 0.005).

Komplikationen bei Kalziuminfusion und akute Hyperkalzämie

Lloyd [173] hat vor etwa 60 Jahren in dramatischer Weise seine eigenen Erfahrungen mit einer Uberdosis Kalzium beschrieben. Als ihm zuerst eine Testmenge Kalziumchlorid (50 ml 1%) injiziert wurde, stieg seine Herzfrequenz an. Als er danach Kalziumchlorid (200 mg) als Bolusinjektion erhielt, wurde ihm schwindlig; er erlitt eine Synkope und eine akute Atemnot. Das EKG zeigte einen SA-Block und eine ausgepragte Bradykardie. Weitere wichtige Informationen werden in Lloyd’s Bericht nicht gegeben: Einige Schlage auf das Abdomen und den Brustkorb haben jedoch ausgereicht, um ihn wiederzubeleben. Sinusarrhythmien und Bradykardien nach Kalziuminfusionen sind mehrfach beschrieben worden [37, 45, 251].

Klinische Indikationen für Kalzium

Kalzium wird im Operationssaal und auf der Intensivstation hauptsachlich aus 3 Grunden eingesetzt. Am haufigsten soll mit diesem Medikament die Herz-Kreislauf-Situation, unabhangig davon, ob nun eine Hypokalzamie besteht oder nicht, verbessert werden [2, 51,93,126,138, 273, 274]. Bei unerwunschten Nebenwirkungen von Kalziumantagonisten [58,112,113,215] und zur Behandlung einer hypokalzamischen Tetanie [67] wird Kalzium ebenfalls eingesetzt. In diesem Zusammenhang soll noch einmal daraufhingewiesen werden, das die klassischen Zeichen oder Symptome einer hypokalzamischen Tetanie oft schwierig zu erkennen sind [33, 95, 139, 161, 248, 275, 284]. Um einen Eindruck uber die klinische Anwendung von Kalzium in einem grosen Spital zu bekommen, haben wir nachgeforscht, wie die 40000 Kalziumchloridampullen, die in der Apotheke des Massachusetts General Hospital jahrlich hergestellt werden, verbraucht werden. 2500 davon werden fur den intraoperativen Gebrauch bei Herzoperationen (ca. 1200/Jahr), 5000 fur den Gebrauch bei anderen operativen Eingriffen (ca. 22 000/Jahr) verwendet.

Elektromechanische Koppelung durch Kalziumionen

Kalzium ist zur elektromechanischen Koppelung in allen Muskeln, sowohl Skelett-, Herz- als auch der glatten Muskulatur, notig [80, 83, 85,119,159–161,295]. Die Skelettmuskulatur ist nicht so stark vom extrazellularen Kalzium abhangig. Selbst in einem kalziumfreien Medium bleibt ihre Kontraktionsfahigkeit wahrend mehrerer Stunden erhalten [295].

Wirkung von Kalziumionen auf das Herz und den Kreislauf

Ein erhohter Kalziumgehalt im Blut oder in der Perfusionslosung fuhrt zu einer Erhohung der Kontraktilitat des Herzmuskels, eine Verminderung des Kalziumgehalts fuhrt zu einer Abnahme der Kontraktilitat. Dies wurde in unzahligen Arbeiten am Papillarmuskel [31, 294], am isolierten Herzen [82,152,185], im Tierexperiment mit konstant gehaltener peripherer Zirkulation (Bypass) [27,71,96], am intakten Tier [189,240,250] und am Menschen [50, 126] gezeigt.

Das kalziumselektive Elektrodensystem

Die Kalziumelektrode ist nicht ionenspezifisch, sondern nur ionenselektiv. Deshalb schrankt das Vorhandensein anderer Kationen die Empfindlichkeit dieser Elektrode gegenuber den Kalziumionen ein.