F.Toraman MD, E.A.Kopman MD, Ümit Çalışırişçi MD, et al.

Department of Anesthesiology

Siyami Ersek Thoracic and Cardiovascular Surgery Center

Istanbul Turkey

Nitroglycerin has been the drug of choice for relieving myocardial ischemia for more than a hundred years. Several studies have indicated that a significant reduction in arterial oxygen tension (PaO₂) occurs after the administration of sublingual nitroglycerin to patients with coronary artery disease breathing room air. Because available oxygen in arterial blood is reduced, it would be reasonable to assume that oxygen delivery to the myocardium would also be impaired. The purpose of this study was to investigate whether nitroglycerin induced arterial desaturation results in compromised oxydative metabolism of myocardium assessed by coronary sinus lactate concentration and oxygen content in patients with coronary artery disease undergoing coronary artery bypass surgery.

Participants: Ten randomly selected patients undergoing coronary bypass surgery.

Setting: All studies were performed at Siyami Ersek Cardiovascular and Thoracic Surgery Center.

Methods: A catheter was inserted into the radial artery to measure blood gases and arterial lactate concentration. After sternotomy, and aortic and venous cannula placement, a coronary sinus catheter was introduced into the coronary sinus to measure oxygen content and lactate concentration. Control coronary sinus and arterial blood samples were obtained before nitroglycerin infusion. Nitroglycerin was then given in a dose of 2 mg/kg/min over 5 minutes. At the end of 5 minutes, second samples were obtained from coronary sinus and arterial catheters.

Main Results: It was found that arterial and coronary sinus oxygen tension decreased significantly. Arterial lactate concentration did not change, coronary sinus lactate concentration decreased. Despite a substantial fall in arterial oxygen tension after administration of nitroglycerin, a significant reduction in coronary sinus lactate concentration occurred.

Conclusion: We conclude that nitroglycerin induced hypoxia does not compromise oxidative metabolism of myocardium as can be assessed by a concomitant decrease in coronary sinus lactate concentration.

nitroglycerin, coronary sinus lactate, hypoxemia, coronary artery bypass

Nitroglycerin has been the drug of choice for relieving myocardial ischemia for more than hundred years (1). Intravenous nitroglycerin has been used during anesthesia to control hypertension and avoid myocardial ischemia before (2,3), during (4-9), and after surgery (10) in patients undergoing myocardial revascularization

Arterial oxygen tension decreases after administration of nitroglycerin in both normal subjects and in patients with coronary artery disease. (11). The reduction of PaO₂ after nitroglycerin would seem to be related to hemodynamic changes that occur after its administration (11,12,13). The clinical importance of observed decline in arterial oxygen tension is evident, since optimal arterial oxygen concentration is vitally important to the maintenance of adequate myocardial oxygenation.

Because the available oxygen in arterial blood is reduced, it would be reasonable to assume that oxygen delivery to the myocardium would also be impaired. But the effect of nitroglycerin induced hypoxia on coronary sinus lactate concentration and oxygen saturation that may be used as metabolic marker of ischemia, has not previously been studied in patients with coronary artery disease. The purpose of this study was to investigate the effect of nitroglycerin induced arterial desaturation on coronary sinus lactate concentration and oxygen content in patients with coronary artery disease undergoing coronary artery bypass surgery (CABG).

After informed consent was obtained eight male and two female patients (mean age 57 ± 9.5 years) were studied according to a protocol approved by the Human Subjects Committee.

All patients had angiographically proven coronary artery disease; (4 patients with four vessel diseases, 5 patients with 3 vessel disease and 1 patient with one vessel disease) were scheduled for elective coronary artery bypass grafting within 4 weeks after diagnostic cardiac catheterisation. All patients were in sinus rhythm and had good ventricular function with ejection fraction greater than 50% at the time of catheterisation. Patients with diabetes mellitus, valvular heart disease, arterial hypertension (diastolic blood pressure > 105 mmHg) significant pulmonary disease, left ventricular end diastolic pressure (LVEDP) >20 mmHg at rest and patients with myocardial infarction within 2 weeks of surgery were excluded from the study. After receiving their routine nitrate, b blocker and calcium channel blocker medication, the patients were premedicated with 10 mg morphine and 0.5 mg scopolamine intramuscularly 60 minutes before induction of anesthesia. A 20 gauge cannula was inserted into the right radial artery for blood sampling and monitoring arterial blood pressure. pH, PaCO₂, PaO₂, O₂ content and hemoglobin were measured with Radiometer Copenhagen ABL605 blood gas analyzer. Saturation was obtained from PaO₂ and pulse oxymetry. A Swan-Ganz thermodilution catheter was inserted percutaneously into the pulmonary artery via the right internal jugular vein for the measurement of mean pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP) and cardiac output (CO). LVSWI (left ventricular stroke work index) has been calculated using standard formula. ECG lead II and V were also recorded. All pressures were monitored continuously with Horizon XL Mennen Medical Inc..

Anesthesia was induced with fentanyl 33 mg /kg preceded by pancuronium bromide 0.02 mg/kg. Pancuronium bromide 0.08 mg/kg was given to facilitate tracheal intubation. Patients were ventilated mechanically with a tidal volume of 5 ml /kg and 25% of oxygen (according to the study protocol). FiO₂ was held constant. A coronary sinus catheter (Retroplegia^@ 14 F, Research medical, Inc., Midvale, Utah) was inserted by the surgeon just prior to cardiopulmonary bypass (CPB). Correct position was confirmed by palpation, visual inspection and a reduced blood oxygen saturation relative to mixed venous blood. Control coronary sinus and arterial blood samples were obtained before nitroglycerin infusion 2 mg/kg/min. At the end of 5 minutes second samples were taken. Heart rate (HR), mean systemic arterial pressure (MAP), CVP, MPAP and PCWP were monitored continuously. Cardiac output was measured by thermodilution with Abbott 3300 CO computer. Hemodynamic measurements, arterial lactate and coronary sinus lactate were obtained simultaneously at two time points, immediately before nitroglycerin infusion and five minutes after the nitroglycerin infusion. Coronary lactate levels were measured by using lactate analyser (Analox LM5 Lactate Analyzer, Analox Instruments Ltd. London). Paired t-test was used for statistical analysis.

Hemodynamic data before and after the nitroglycerin administration are shown in table 1. After nitroglycerin infusion HR increased from 79.8± 7.4 to 87.3± 11.8 beat/min (p <0.05); MAP decreased from a control value 87.8± 9.4 to 65.8± 10.3 mmHg (p<0.01); CVP fell from 4.6± 2.7 to 1.4± 1.5 mmHg (p<0.01), MPAP fell from 12.7± 4.1 to 8.7± 3.4 mmHg (p<0.01), PCWP dropped from 5.5± 2.9 to 3.0± 2.1 mmHg (p<0.01); CI decreased from 2.68± 0.5 to 2.31± 0.6 L/min/m² (p<0.01)

PaO₂ (Table 2) decreased from a control value 108.3± 21.5 to 64.4± 11 mmHg (p<0.01); arterial blood oxygen content fell from 18.0± 2.0 to 15.2± 2.1 ml/100ml (p<0.01); arterial blood, pH, PCO₂ and hemoglobin are not significantly changed. Arterial blood lactate concentration did not changed significantly.

Coronary sinus PO₂ decreased from 22.1± 8.5 to 19.2± 6.3 mmHg. (p<0.01). Coronary sinus oxygen content decreased from 5.9± 3.7 to 5.0± 3.1 ml/100ml. (p<0.01) Coronary sinus lactate decreased from 1.3± 0.5 to 1.1± 0.5 mmol/L (p<0.01)(See table 3.)

ST segment did not change following the administration of nitroglycerin.

Table 1: Hemodynamic Responses to Intravenous Nitroglycerin in Patients Undergoing Myocardial Revascularization

Table 2 Arterial Blood Gases and Lactate Concentration Changes

PaO₂: Arterial oxygen tension; PaCO₂: Arterial carbon dioxide tension;
Oct (a): Arterial oxygen content; Hb: Hemoglobin; Lactate(a):Arterial lactate concentration

Table 3: Coronary Sinus Blood Gases and Lactate Concentration Changes

PCO₂(cs): coronary sinus carbon dioxide tension; PO₂(cs): Coronary sinus oxygen tension; Oct(cs):Coronary sinus oxygen content; Lactate(cs):Coronary sinus lactate concentration

Discussion:

Previous studies have showed that a significant reduction in arterial oxygen tension (PaO₂) occurs after the administration of sublingual nitroglycerin to patients with coronary artery disease breathing room air (10) Reduction in PaO₂ following administration of sublingual nitroglycerin can be attributed to:1) vasodilatation in poorly ventilated areas of the lung; 2) a relative increase in perfusion in the dependent less ventilated parts of the lung due to the fall in pulmonary artery pressure; 3) a decrease in cardiac output and, 4) an increase in intrapulmonary shunt (8).

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