Nitroglycerin-induced hypoxemia does not produce myocardial ischemia

Nitroglycerin-Induced Hypoxemia Does Not Produce Myocardial Ischemia Fevzi Toraman, MD, Ercfiment A. Kopman, MD, I~lmit Cali#iri#£i, MD, Murat Demirta#, MD, Fuat Bilgen, MD, Azmi Ozler, MD, Sevim Canik, MD, and Besim Yi(3iter, MD Objective: 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 (Pa02) 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 oxidative 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 pg/kg/min for a period of 5 minutes. At the end of 5 minutes, second samples were obtained from the 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: Nitroglycerin-induced hypoxia does not compromise oxidative metabolism of myocardium as can be assessed by a concomitant decrease in coronary sinus lactate concentration.

ITROGLYCERIN has been the drug of choice for relieving myocardial ischemia for more than one hundred years.J Intravenous nitroglycerin has been used during anesthesia to control hypertension and to avoid myocardial ischemia before, 2,3 during, 4-9 and after surgery 1° in patients undergoing myocardial revascularization Arterial oxygen tension decreases after administration of nitroglycerin in both normal subjects and in patients with coronary artery disease, u The reduction of PaO2 after nitroglycerin would seem to be related to hemodynamic changes that occur after its administration, n-13 The clinical importance of observed decline in arterial oxygen tension is evident, because 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, which may be used as a 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 grafting (CABG).

four patients had four-vessel disease, five patients had three-vessel disease, and one patient had one-vessel disease. They were scheduled for elective CABG within 4 weeks after diagnostic cardiac catheterization. All patients were in sinus rhythm and had good ventricular function, with ejection fraction greater than 50% at the time of catheterization. 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, [3-blocker, and calcium channel blocker medication, the patients were premedicated with 10 mg of morphine and 0.5 mg of 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, 02 content, and hemoglobin were measured with an ABL605 blood gas analyzer (Radiometer A/S Emdrupvej 72 DK-2400, Copenhagen, Denmark). Saturation was obtained from PaO2 and pulse oximetry. A Swan-Ganz thermodilution catheter was inserted percutaneously into the pulmonary artery through 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) was calculated using standard formula. ECG leads II and V were also

N

METHOD 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;

Journal of Cardiothoracic and Vascular Anesthesia,

Copyright © 1997 by W,B. Saunders Company KEY WORDS: nitroglycerin, coronary sinus lactate, hypoxemia, coronary artery bypass

From the Departments of Anesthesiology and Cardiovascular Surgery, Siyami Ersek Thoracic and Cardiovascular Surgery Center, lstanbul Turkey. Address reprint requests to Fevzi Toraman, MD, Barbaros Mah. Tophanelio~lu Cad, Petek Sitesi, A 5 Blok, D: 20, 81190, ()skiidar, Istanbul, Turkey. Copyright © 1997 by W.B. Saunders Company 1053-0770/97/1107-001053.00/0

Vol 11, No 7 (December),1997:pp 861-863

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TORAMAN ET AL

recorded. All pressures were monitored continuously with Horizon XL (Mennen Medical Ltd, Rehovot, Israel). Anesthesia was induced with fentanyi, 33 ~tg/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). Fraction of inspired oxygen (FIO2) was held constant. A coronary sinus catheter (Retroplegia 14-F, Research Medical, Inc, Midvale, UT) was inserted by the surgeon just before 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 pg/kg/ rain. At the end of 5 minutes, second samples were taken. Heart rate (HR), mean systemic arterial pressure (MAP), CVR MPAP, and PCWP were monitored continuously. Cardiac output was measured by thermodilution with an Abbott 3300 CO computer (Abbott Laboratories, North Chicago, IL). Hemodynamic measurements, arterial lactate, and coronary sinus lactate were obtained simultaneously at two time points, immediately before nitroglycerin infusion and 5 minutes after the nitroglycerin infusion. Coronary lactate levels were measured by using a lactate analyzer (Analox LM5 Lactate Analyzer, Analox Instruments Ltd, London). Paired t-test was used for statistical analysis. RESULTS

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 beats/min (p < 0.05); MAP decreased from a control value of 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); and cardiac index decreased from 2.68 _+ 0.5 to 2.31 _+ 0.6 L/min/m 2 (p < 0.01) PaO2 (Table 2) decreased from a control value of 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 were 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

Table 1. Hemodynamic Responses to Intravenous Nitroglycerin in Patients Undergoing Myocardial Revascularization Before NTG mean ± SD

After NTG mean _+SD

HR (beat/min) 79.8-+7.4 87.3-+11.8 MAP (mmHg) 87.8 -+ 9.4 65.8 -+ 10.3 MPAP (mmHg) 12.7 -+ 4.1 8.7 -+ 3.4 PCWP (mmHg) 5.5 -+ 2.9 3.0 -+ 2.1 CVP (mrnHg) 4.6 -+ 2.7 1.4 -+ 1.5 CI (L/min/m 2) 2.68 -+ 0.5 2.31 + 0.6 LVSWI (g-m/beat/m 2) 37.40 -+ 9.46 21.30 -+ 5.5 RPP 10,066.1 -+ 1,673.3 8,077.2 -+ 1,379.3

pValue p p p p p p p p

< < < < < < < <

0.05 0.01 0.01 0.01 0.01 0.01 0.01 0.01

Abbreviations: HR, heart rate; MAP, mean arterial pressure; MPAP' mean pulmonary arterial pressure; PCWP' pulmonary capillary wedge pressure; CVP' central venous pressure; CI, cardiac index; NTG, nitroglycerin; RPP, rate-pressure product; LVSWI, left ventricular stroke work index.

Table 2. Arterial Blood Gases and Lactate Concentration Changes Before NTG mean _+SD

After NTG mean _+SD

pValue

pH

7.36 + 0.04

7.35 _+ 0.04

NS

PaCO2 (mmHg)

38.1 -+ 6.1

39.9 -+ 6.1

NS

108,3-+21.5

64.4-- 11

p < 0.01

PaO2 (mmHg) Oct (a) (mL/100 mL)

18.0-+2.0

15.2_+2.1

p < 0.01

Hb (gr/dL)

13~5 _+ 0.8

12.6 -+ 1

p < 0.01

Lactate(a) (mmol)

0.8 _+ 0.2

0.9 -+ 0.2

NS

Abbreviations: PaO2, arterial oxygen tension; PaCO2, arterial carbon dioxide tension; Oct (a), arterial oxygen content; Hb, hemoglobin; Lactate(a), arterial lactate concentration.

from 5.9 + 3.7 to 5.0 -+ 3.1 mL/100 mL (p < 0.01). Coronary sinus lactate decreased from 1.3 .+ 0.5 to 1.1 - 0.5 mmol/L (p < 0.01)(Table 3.) ST segments on the ECG did not change following the administration of nitroglycerin. DISCUSSION

Previous studies have shown 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.l° Reduction in PaO2 after administration of sublingual nitroglycerin can be attributed to vasodilation in poorly ventilated areas of the lung, a relative increase in perfusion in the dependent, less ventilated, parts of the lung caused by a decrease in pulmonary artery pressure, a decrease in cardiac output, and an increase in intrapulmonary shunt. 8 The clinical importance of observed change in arterial oxygen tension is evident because optimal arterial oxygen tension is vitally important for the maintenance of adequate myocardial oxygenation. In critically ill patients with coronary artery disease and myocardial ischemia, a decline in available oxygen may offset the beneficial effect of nitroglycerin. The present study showed that, despite a significant reduction in arterial oxygen tension, coronary sinus lactate concentration did not increase; rather, it significantly decreased. Despite a significant reduction in PaO2, metabolic integrity of the myocardium did not change, as reflected by an improved lactate extraction. It is possible that the reduced oxygen consumption caused by concomitant decreases in preload, afterload, rate-pressure product, and LVSWI may explain the persistent beneficial effect of nitroglycerin. It was concluded that nitroglycerin-induced hypoxia does not produce myocardial ischemia. Table 3. Coronary Sinus Blood Gases and Lactate Concentration Changes Before NTG mean _+SD pH(cs) PCO2{cs) (mmHg) PO2(cs) (mmHg) Oct(cs) (mL/100 mL) Lactate(cs) (mmol/L)

7.32 51.9 22.1 5.9 1.3

-+ 0.03 -+ 6.2 + 8.5 -- 3.7 _+ 0.5

After NTG mean ± SD 7.31 52.2 19.2 5.0 1.1

_+ 0.03 -+ 6.6 _+ 6.3 -+ 3.1 _+ 0.5

pValue p < 0.01 NS p < 0.03 p < 0.04 p < 0.01

Abbreviations: 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.

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