Hyperoxic ventilation at the critical hematocrit: effects on myocardial perfusion and function.

BACKGROUND: Hemodilution reduces hematocrit (Hct) and blood oxygen content. Tissue oxygenation is mainly preserved by increased cardiac output. As myocardial O2-demands increase, coronary vasodilatation becomes necessary to increase myocardial blood flow. Myocardial ischemia occurs at a critical Hct-value (Hctcrit), with accompanying exhaustion of coronary reserve. Hyperoxic ventilation is known to both reverse peripheral tissue hypoxia at Hctcrit and also to induce coronary vasoconstriction. This study aimed to determine whether hyperoxic ventilation at Hctcrit further exacerbates myocardial ischemia and dysfunction. METHODS: Nine anesthetized pigs ventilated on room air were hemodiluted by 1:1 exchange of blood with pentastarch (6%HES) to Hctcrit, defined as onset of myocardial ischemia (ECG changes). At Hctcrit, hyperoxic ventilation was started. Measurements were performed at baseline, at Hctcrit, and after 15 min of hyperoxic ventilation. We determined myocardial blood flow (microsphere method), arterial O2-content, subendocardial O2-delivery and myocardial function (left ventricular pressure increase). RESULTS: At Hctcrit 7 (6;8)%, O2-content was reduced [3.7 (3.1;3.9) ml dl(-1)]. Despite a compensatory increase of myocardial blood flow [531 (449;573), ml min(-1)100 g(-1)], all pigs displayed myocardial ischemia and compromised myocardial function (P < 0.05). Hyperoxic ventilation produced increased coronary vascular resistance secondary to vasoconstriction, and reduced myocardial blood flow [426 (404;464), ml min(-1)100 g(-1); P < 0.05]. Myocardial oxygenation was found to be maintained by increased O2-content [4.4 (4.2;4.8), ml dl(-1); P < 0.05], the contribution of dissolved O2 to subendocardial O2-delivery increased (32 vs. 8%; P < 0.05), which preserved myocardial function. CONCLUSION: Hyperoxic ventilation at Hctcrit is followed by coronary vasoconstriction and reduction of coronary blood flow. However, myocardial oxygenation and function is maintained, as increased O2-content (in particular dissolved O2) preserves myocardial oxygenation.

Hyperoxic ventilation at the critical haematocrit.

OBJECTIVE: During normovolaemic haemodilution arterial O(2)-content decreases exponentially. Nevertheless, tissue oxygenation is first maintained initially by increased organ perfusion and O(2)-extraction. As soon as these compensatory mechanisms are exhausted, myocardial ischaemia and tissue hypoxia occur at an individual 'critical' haematocrit (Hct) value. This study was conducted in order to assess whether tissue hypoxia at the critical Hct is reversed by hyperoxic ventilation with 100% O(2). METHOD: Eighteen anaesthetized pigs were ventilated with room air and were hemodiluted by 1:1 exchange of blood with 6% pentastarch to their individual critical Hct (onset of myocardial ischaemia; significant ECG changes). At the critical Hct, hyperoxic ventilation was initiated. In nine complete datasets, global O(2) delivery and consumption, local tissue O(2) partial pressure (tpO(2)) (MDO-Electrode, Eschweiler, Kiel, Germany) and organ blood flow (microsphere method) in skeletal muscle were analyzed at baseline, after haemodilution to the critical Hct and after 15 min of hyperoxic ventilation. RESULTS: At the critical Hct (7.2+/-1.2%), tpO(2) was reduced from 23+/-3 to 10+/-2 Torr with 50% of all values in the hypoxic range (<10 Torr, all P<0.05). During hyperoxic ventilation, contribution of physically dissolved O(2) to the O(2) delivery and O(2) consumption increased by 400 and 563% (P<0.05) and instantly restored tpO(2) to 18+/-2 Torr, (hypoxic values 25%, P<0.05). CONCLUSION: Hyperoxic ventilation reversed tissue hypoxia at the critical Hct due to preferential utilization of plasma O(2) and allowed temporary preservation of tissue oxygenation. During haemodilution, hyperoxic ventilation might offer an effective bridge until red cells are ready for transfusion.

Calculation is unsuitable for determination of O2-consumption (VO2) in case of O2-supply-dependency.

BACKGROUND: When O2-delivery to tissues is critically reduced, O2-consumption becomes dependent on O2-delivery and starts to decline, which reflects tissue hypoxia. In order to timely detect tissue hypoxia prior to organ damage, O2-consumption may be calculated or measured from respiratory gases. We have assessed reproducibility of calculated and measured O2-consumption-data and their agreement during O2-supply-dependency. METHOD: Data of 31 anesthetized, ventilated pigs were analysed retrospectively. Animals had undergone either controlled hemorrhage ("shock") or isovolemic exchange of blood with colloids (extreme hemodilution, "HD") until O2-consumption had become dependent on O2-delivery. O2-consumption was calculated from the Fick equation and measured simultaneously with a DELTATRAC II metabolic monitor. Repeatability was determined for (1) calculated and (2) for measured.VO2 -values and (3) for input variables of the Fick equation (i.e. cardiac index (CI) and arteriovenous O2-content difference (CaO2-CvO2)). Bias between calculated and measured data and precision of calculation were assessed from paired O2-consumption-values obtained before and after induction of O2-supply-dependency via hemorrhage or extreme hemodilution. RESULTS: Repeatability of the reversed Fick method was inferior to repeatability of measurement (27 vs 15%) due to error propagation from CI and (CaO2-CvO2). Between-method-bias at baseline ("BL") was 3%, and changed in case of O2-supply-dependency (shock -15%; HD -31%, both p<0.05 vs BL), precision of the reversed Fick method deteriorated (BL 32%; shock 60%; HD 60%) due to variability of CI (CV: 16%; shock 27%; HD 41%). CONCLUSION: In anesthetized pigs calculated and measured O2-consumption values are in agreement, while in presence of O2-supply-dependency the reversed Fick method (1) grossly underestimates true O2-consumption and (2) precision deteriorates not allowing to verify or reject the presence of tissue hypoxia.

Changes in p(i)CO(2) reflect splanchnic mucosal ischaemia more reliably than changes in pH(i) during haemorrhagic shock.

BACKGROUND: Gastric tonometry is intended to reveal alterations in splanchnic perfusion and oxygenation. Based on the tonometric measurement of gastric mucosal partial pressure of carbon dioxide (pCO(2)) and the simultaneous determination of arterial blood gas parameters (bicarbonate concentration [HCO(3-)], pH and pCO(2)), several parameters can be calculated. AIMS: To identify the most suitable tonometric parameter [gastric mucosal pH (pH(i)), intramucosal pCO(2) (p(i)CO(2)), the difference between tonometric and arterial pCO(2) concentrations (pCO(2) gap), [H+] gap] that reliably reflects gastric hypoperfusion and hypoxia during severe haemorrhagic shock. DESIGN: Randomised, controlled experimental study. METHODS: An artificial stenosis of the left anterior descending coronary artery (LAD) was induced. Subsequently, the animals were haemorrhaged to a mean arterial pressure of 45 mmHg, which was maintained for 60 min. MEASUREMENTS AND MAIN RESULTS: Tonometric measurements were performed in 17 land-race pigs before and after induction of LAD stenosis and after haemorrhagic shock. P values obtained using the Wilcoxon signed-rank testing were used to compare the level of significance for the tonometric parameters and the corresponding arterial blood gas values [arterial pCO2 (p(a)CO(2)), [HCO(3-)], arterial pH (pH(a))]. While induction of critical coronary stenosis did not provoke any changes, all parameters changed significantly during haemorrhagic shock. The lowest P value was found for pH(i) (P=0.00013) followed by [H+ gap] (P=0.0005). P values higher by a factor of ten were found for pCO(2) gap (P=0.00119) and were highest for p(i)CO(2) (P=0.00562). P values of the corresponding arterial blood gas parameters were lower by a factor of ten than the P value of p(i)CO(2). CONCLUSION: pH(i), pCO(2) gap and [H+] gap are considerably influenced by changes of systemic arterial blood gas values. This is demonstrated by lower P values of the corresponding arterial blood gas values in comparison with p(i)CO(2). Therefore pH(i), pCO(2) gap and [H+] gap seem to indicate more likely systemic changes, whereas p(i)CO(2) appears to reflect disturbances of regional gastric tissue perfusion and oxygenation more reliably than any other derived tonometric parameter.

Diaspirin crosslinked hemoglobin enables extreme hemodilution beyond the critical hematocrit.

BACKGROUND: Normovolemic hemodilution is an effective strategy to limit perioperative homologous blood transfusions. The reduction of hematocrit related to hemodilution results in reduced arterial oxygen content, which initially is compensated for by an increase in cardiac output and oxygen extraction ratio. To increase the efficacy of hemodilution, a low hematocrit should be aimed for; however, this implies the risk of myocardial ischemia and tissue hypoxia. OBJECTIVE: To assess whether hemodilution can be extended to lower hematocrit values by the use of a hemoglobin-based artificial oxygen carrier solution. DESIGN: Prospective, randomized, controlled. SETTING: Animal laboratory of a university hospital. SUBJECTS: Twelve anesthetized, mechanically ventilated pigs. INTERVENTIONS: Isovolemic hemodilution was performed with either 10% diaspirin crosslinked hemoglobin (DCLHb Baxter Healthcare, Boulder, CO; n = 6) or 8% human albumin solution (HSA, oncotically matched to DCLHb, Baxter Healthcare; n = 6) to a hematocrit of 15%, 8%, 4%, 2%, and 1%. MEASUREMENTS AND MAIN RESULTS: In both groups, measurements were performed at baseline at the previously mentioned preset hematocrit values and at the onset of myocardial ischemia characterized by critical hematocrit (significant ST-segment depression >0.1 mV and/or arrhythmia). To determine peripheral tissue oxygenation and myocardial perfusion and function, the following variables were evaluated: total body oxygen transport variables, tissue oxygen partial pressure (tPo2, MDO-Electrode, Eschweiler Kiel, Germany) on the surface of the skeletal muscle, coronary perfusion pressure, left ventricular (LV) end-diastolic pressure, global and regional myocardial contractility (maximal change in pressure over time, LV segmental shortening, microsonometry method), LV myocardial blood flow (fluorescent microsphere technique), LV oxygen delivery, and the ratio between LV subendocardial and subepicardial myocardial perfusion. In the HSA group, critical hematocrit was found at 6.1 (1.8)% (hemoglobin, 2 g x dL(-1)), whereas all DCLHb-treated animals survived hemodilution until hematocrit 1.2 (0.2)% (hemoglobin, 4.7 g x dL(-1)) was achieved without signs of hemodynamic instability. Although arterial oxygen content was higher in the DCLHb group at 1.2% hematocrit than in the HSA group at critical hematocrit (i.e., hematocrit, 6.1%; hemoglobin, 2 g.dL-1) neither oxygen delivery and oxygen uptake nor median tPo2 and hypoxic tPo2 values on the skeletal muscle were different between groups. In contrast, subendocardial ischemia was absent in DCLHb-diluted animals until 1.2% hematocrit was achieved. This was attributable to a higher coronary perfusion pressure (65 (22) mm Hg vs. 19 (8) mm Hg; p <.05), higher subendocardial perfusion (4.1 (2.6) mL.min-1.g-1 vs. 1.2 (0.4) mL x min(-1) x g(-1)), and subendocardial oxygen delivery (5.7 (2) mL x min(-1) x g(-1), p <.05) in DCLHb-diluted animals, resulting in superior myocardial contractility reflected by maximal change in pressure over time (3829 (1914) vs. 1678 (730); p <.05) and higher regional myocardial contractility (11 (8)% vs. 6 (2)%; p <.05). An increased LV end-diastolic pressure reflected LV myocardial pump failure in HSA-diluted animals but was unchanged in DCLHb-diluted animals. In the DCLHb group, systemic vascular resistance index remained at baseline values throughout the protocol, whereas coronary vascular resistance decreased. In contrast, both variables decreased in HSA-diluted animals. CONCLUSION: DCLHb as a diluent allowed for hemodilution beyond the hematocrit value, determined "critical" after hemodilution with HSA (6.1% (1.8)%). Even at 1.2% hematocrit (hemoglobin, 4.7 g x dL(-1)) myocardial perfusion and function were maintained, although at the expense of peripheral tissue oxygenation. This discrepancy in regional oxygenation might be caused by a redistribution of blood flow favoring the heart, which is related to a disproportionate decrease of coronary vascular resistance index during hemodilution with DCLHb.