Impact of intermittent apnea on myocardial tissue oxygenation--a study using oxygenation-sensitive cardiovascular magnetic resonance

Dominik P Guensch, Kady Fischer, Jacqueline A Flewitt, Matthias G Friedrich, Dominik P Guensch, Kady Fischer, Jacqueline A Flewitt, Matthias G Friedrich

Abstract

Background: Carbon dioxide (CO(2)) is a recognized vasodilator of myocardial blood vessels that leads to changes in myocardial oxygenation through the recruitment of the coronary flow reserve. Yet, it is unknown whether changes of carbon dioxide induced by breathing maneuvers can be used to modify coronary blood flow and thus myocardial oxygenation. Oxygenation-sensitive cardiovascular magnetic resonance (CMR) using the blood oxygen level-dependent (BOLD) effect allows for non-invasive monitoring of changes of myocardial tissue oxygenation. We hypothesized that mild hypercapnia induced by long breath-holds leads to changes in myocardial oxygenation that can be detected by oxygenation-sensitive CMR.

Methods and results: In nine anaesthetized and ventilated pigs, 60s breath-holds were induced. Left ventricular myocardial and blood pool oxygenation changes, as monitored by oxygenation-sensitive CMR using a T2*-weighted steady-state-free-precession (SSFP) sequence at 1.5T, were compared to changes of blood gas levels obtained immediately prior to and after the breath-hold. Long breath-holds resulted in an increase of paCO(2), accompanied by a decrease of paO(2) and pH. There was a significant decrease of blood pressure, while heart rate did not change. A decrease in the left ventricular blood pool oxygenation was observed, which was similar to drop in SaO(2). Oxygenation in the myocardial tissue however, was maintained throughout the period. Changes in myocardial oxygenation were strongly correlated with the change in paCO(2) during the breath-hold (r = 0.90, p = 0.010).

Conclusion: Despite a drop in blood oxygen levels, myocardial oxygenation is maintained throughout long breath-holds and is linearly correlated with the parallel increase of arterial CO(2), a known coronary vasodilator. Breathing maneuvers in combination with oxygenation-sensitive CMR may be useful as a diagnostic test for coronary artery function.

Conflict of interest statement

Competing Interests: Matthias G. Friedrich is advisor and shareholder of Circle Cardiovascular Imaging Inc., Calgary, AB, Canada. There is a pending patent (US Patent Pending 61_680,981), which protects the use of breathing maneuvers to induce changes of myocardial oxygenation for diagnostic purposes. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Myocardial and blood pool SI…
Figure 1. Myocardial and blood pool SI throughout the cardiac cycle.
The area under the curve was calculated from the absolute BOLD-SI values of the 20 phases of the cardiac cycle from images obtained at the start and at the end of a breath-hold of both the myocardium (A) and blood pool (B) of one subject.
Figure 2. Change in arterial blood pool…
Figure 2. Change in arterial blood pool and myocardial tissue oxygenation during a 60 seconds breath-hold.
Phase 11 of the cardiac cycle representing end-systole is presented for both the image from baseline (B) and the end of the breath-hold (C). The analyzed myocardial region is outlined on the BOLD-CMR image by the endocardial (red) and epicardial (green) contours resulting in a trend toward a mean SI increase (+4.8%; p = 0.077, n = 6) (A). The orange contour depicts a region of interest in the blood pool, with a significant mean SI decrease (-8.0%; p = 0.047).
Figure 3. Correlation of myocardial SI in…
Figure 3. Correlation of myocardial SI in oxygenation-sensitive CMR images to changes in paCO2.
Differences in paCO2 (mmHg) are plotted against the % change in myocardial SI (n = 6). The data shows excellent linear correlation (r = 0.90, p = 0.010). The dashed lines represent the 95% confidence interval.

References

    1. Ainslie PN, Poulin MJ (2004) Ventilatory, cerebrovascular, and cardiovascular interactions in acute hypoxia: regulation by carbon dioxide. J Appl Physiol 97: 149–159 doi:.
    1. Kety SS, Schmidt CF (1948) The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood flow and cerebral oxygen consumption of normal young men. J Clin Invest 27: 484–492.
    1. Beaudin AE, Brugniaux JV, Vohringer M, Flewitt J, Green JD, et al.. (2011) Cerebral and myocardial blood flow responses to hypercapnia and hypoxia in humans. Am J Physiol Heart Circ Physiol. Available: . Accessed 27 September 2011.
    1. Case RB, Greenberg H (1976) The response of canine coronary vascular resistance to local alterations in coronary arterial P CO2. Circ Res 39: 558–566 doi:.
    1. Bauer WR, Nadler W, Bock M, Schad LR, Wacker C, et al. (1999) The relationship between the BOLD-induced T(2) and T(2)(*): a theoretical approach for the vasculature of myocardium. Magn Reson Med 42: 1004–1010.
    1. Wacker CM, Bock M, Hartlep AW, Beck G, van Kaick G, et al... (1999) AID-MRM6>;2–9.
    1. Friedrich MG, Niendorf T, Schulz-Menger J, Gross CM, Dietz R (2003) Blood oxygen level-dependent magnetic resonance imaging in patients with stress-induced angina. Circulation 108: 2219–2223 doi:.
    1. Ogawa S, Lee TM, Kay AR, Tank DW (1990) Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc Natl Acad Sci USA 87: 9868–9872.
    1. Vöhringer M, Flewitt JA, Green JD, Dharmakumar R, Wang J Jr, et al. (2010) Oxygenation-sensitive CMR for assessing vasodilator-induced changes of myocardial oxygenation. J Cardiovasc Magn Reson 12: 20 doi:.
    1. Dharmakumar R, Qi X, Hong J, Wright GA (2006) Detecting microcirculatory changes in blood oxygen state with steady-state free precession imaging. Magn Reson Med 55: 1372–1380 doi:.
    1. Varjavand N (2000) Oxyhemoglobin Dissociation Curve. Available: . Accessed 2012 Aug 7.
    1. Severinghaus JW (1979) Simple, accurate equations for human blood O2 dissociation computations. J Appl Physiol 46: 599–602.
    1. Kelman GR (1966) Digital computer subroutine for the conversion of oxygen tension into saturation. J Appl Physiol 21: 1375–1376.
    1. Bauer WR, Nadler W, Bock M, Schad LR, Wacker C, et al. (1999) Theory of coherent and incoherent nuclear spin dephasing in the heart. Phys Rev Lett 83: 4215–4218 doi:.
    1. Kassab GS, Lin DH, Fung YC (1994) Morphometry of pig coronary venous system. Am J Physiol Heart Circ Physiol 267: H2100–H2113.
    1. Kuo L, Chancellor JD (1995) Adenosine potentiates flow-induced dilation of coronary arterioles by activating KATP channels in endothelium. Am J Physiol 269: H541–549.
    1. Wacker CM, Hartlep AW, Pfleger S, Schad LR, Ertl G, et al. (2003) Susceptibility-sensitive magnetic resonance imaging detects human myocardium supplied by a stenotic coronary artery without a contrast agent. J Am Coll Cardiol 41: 834–840 doi:.
    1. Fieno DS, Shea SM, Li Y, Harris KR, Finn JP, et al. (2004) Myocardial perfusion imaging based on the blood oxygen level-dependent effect using T2-prepared steady-state free-precession magnetic resonance imaging. Circulation 110: 1284–1290 doi:.
    1. Manka R, Paetsch I, Schnackenburg B, Gebker R, Fleck E, et al. (2010) BOLD cardiovascular magnetic resonance at 3.0 tesla in myocardial ischemia. J Cardiovasc Magn Reson 12: 54 doi:.
    1. Atalay MK, Reeder SB, Zerhouni EA, Forder JR (1995) Blood oxygenation dependence of T1 and T2 in the isolated, perfused rabbit heart at 4.7T. Magn Reson Med 34: 623–627.
    1. Shea SM, Fieno DS, Schirf BE, Bi X, Huang J, et al. (2005) T2-Prepared steady-state free precession blood oxygen level–dependent MR imaging of myocardial perfusion in a dog stenosis model. Radiology 236: 503–509 doi:.
    1. Karamitsos TD, Leccisotti L, Arnold JR, Recio-Mayoral A, Bhamra-Ariza P, et al. (2010) Relationship between regional myocardial oxygenation and perfusion in patients with coronary artery disease: insights from cardiovascular magnetic resonance and positron emission tomography. Circ Cardiovasc Imaging 3: 32–40 doi:.
    1. Li D, Dhawale P, Rubin PJ, Haacke EM, Gropler RJ (1996) Myocardial signal response to dipyridamole and dobutamine: Demonstration of the BOLD effect using a double-echo gradient-echo sequence. Magn Reson Med 36: 16–20 doi:.
    1. Arnold JR, Karamitsos TD, Bhamra-Ariza P, Francis JM, Searle N, et al. (2012) Myocardial oxygenation in coronary artery disease: insights from blood oxygen level-dependent magnetic resonance imaging at 3 Tesla. J Am Coll Cardiol 59: 1954–1964 doi:.
    1. Broten TP, Romson JL, Fullerton DA, Winkle DMV, Feigl EO (1991) Synergistic action of myocardial oxygen and carbon dioxide in controlling coronary blood flow. Circulation Research 68: 531–542 doi:.
    1. Alella A, Williams FL, Bolene-Williams C, Katz LN (1955) Interrelation between cardiac oxygen consumption and coronary blood flow. Am J Physiol 183: 570–582.
    1. Hsu YY, Kuan WC, Lim KE, Liu HL (2010) Breathhold-regulated blood oxygenation level-dependent (BOLD) MRI of human brain at 3 tesla. J Magn Reson Imaging 31: 78–84 doi:.
    1. Kannurpatti SS, Biswal BB, Hudetz AG (2002) Differential fMRI-BOLD signal response to apnea in humans and anesthetized rats. Magn Reson Med 47: 864–870 doi:.
    1. Rioja E, Kerr CL, McDonell WN, Dobson H, Konyer NB, et al. (2010) Effects of hypercapnia, hypocapnia, and hyperoxemia on blood oxygenation level-dependent signal intensity determined by use of susceptibility-weighted magnetic resonance imaging in isoflurane-anesthetized dogs. Am J Vet Res 71: 24–32 doi:.
    1. Gauthier CJ, Hoge RD (2012) Magnetic resonance imaging of resting OEF and CMRO(2) using a generalized calibration model for hypercapnia and hyperoxia. Neuroimage 60: 1212–1225 doi:.
    1. Rothe CF, Stein PM, MacAnespie CL, Gaddis ML (1985) Vascular capacitance responses to severe systemic hypercapnia and hypoxia in dogs. Am J Physiol 249: H1061–1069.
    1. Eliades D, Weiss HR (1986) Effect of hypercapnia on coronary circulation. Cardiovasc Res 20: 127–133.
    1. Arellano R, Jiang MT, O’Brien W, Hossain I, Boylen P, et al. (1999) Acute graded hypercapnia increases collateral coronary blood flow in a swine model of chronic coronary artery obstruction. Crit Care Med 27: 2729–2734.
    1. Koehler RC, McDonald BW, Krasney JA (1980) Influence of CO2 on cardiovascular response to hypoxia in conscious dogs. Am J Physiol 239: H545–H558.

Source: PubMed

3
Prenumerera