William W. Holt

Noninvasive evaluation of global left ventricular function with use of cine nuclear magnetic resonance

Previous reports have validated the accuracy of nuclear magnetic resonance (NMR) imaging for quantitating ventricular volumes and myocardial mass. In this study, a new rapid NMR imaging method, cine NMR imaging, was used to compare left ventricular volumes determined from the transverse plane and short-axis plane in healthy volunteers and patients with dilated cardiomyopathy. With use of the short-axis plane, left ventricular mass at end-systole and end-diastole were determined and left ventricular systolic wall thickening at three different levels was assessed. For validation in the current study, cine NMR imaging and two-dimensional echocardiographic measurements of left ventricular volumes were correlated. Left ventricular volumes of the normal volunteers (end-systolic volume = 34 +/- 3.8 ml, end-diastolic volume = 90.4 +/- 7.2 ml) and patients with cardiomyopathy (end-systolic volume = 173 +/- 28.3 ml, end-diastolic volume = 219.5 +/- 29.6 ml) obtained in the transverse plane were nearly identical to those obtained in the short-axis plane (normal volunteers, end-systolic volume = 30.3 +/- 3.5 ml, end-diastolic volume = 84.7 +/- 7.0 ml and patients with cardiomyopathy, end-systolic volume = 179.1 +/- 27.8 ml, end-diastolic volume = 227 +/- 30.9 ml) and correlated highly (r = 0.91) with volumes obtained by two-dimensional echocardiography. Assessment of left ventricular mass over a broad range using cine NMR imaging in a short-axis plane was identical at end-systole (normal volunteers, 117 +/- 10 g; patients with cardiomyopathy, 202 +/- 20 g) and end-diastole (normal volunteers, 115 +/- 10 g; patients with cardiomyopathy, 194 +/- 21 g).(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive determination of left ventricular output and wall stress in volume overload and in myocardial disease by cine magnetic resonance imaging

The current study used cine magnetic resonance imaging to determine the effect of increasing severity of valvular regurgitation on systolic wall stress and to demonstrate that wall stress was disproportionately increased in relation to the severity of regurgitation in patients with myocardial disease. A total of 39 patients with predominantly mitral (n = 22) or aortic (n = 17) regurgitation with (n = 13) and without (n = 26) myocardial disease and 10 normal volunteers were examined with cine magnetic resonance imaging (MRI) at 1.5 T. Left ventricular (LV) cardiac output (CO) and peak systolic (PS) wall stress (WS) and end-systolic (ES) WS were calculated from blood pressure recordings, carotid pulse tracings, and wall thickness (h) and diameter (D) measurements obtained from cine MRI. Patients were classified into three degrees of severity according to their LV regurgitant volume (RV). Myocardial disease was defined by an ejection fraction (EF) of less than 40%. Mean LV EF was 61 +/- 3% in normal volunteers, 64 +/- 3% in patients with regurgitation, and 25 +/- 2% in patients with myocardial disease. LV CO was directly related to RV in patients without myocardial disease, whereas it was disproportionately low in relation to RV in patients with myocardial disease. PS WS was significantly higher in severe mitral and/or aortic regurgitation compared with moderate, mild, and no mitral and/or aortic regurgitation. Compared with the degree of regurgitation, PS WS was disproportionately higher in patients with myocardial disease. Thus LV CO and WS rise progressively with increasing severity of regurgitation. Disproportionately high systolic WS relative to RV indicates the presence of myocardial disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of nicardipine, a calcium antagonist, on myocardial salvage and high energy phosphate stores in reperfused myocardial injury☆

The current study determined the effectiveness of nicardipine, a 1,4-dihydropyridine calcium antagonist, in preserving reperfused myocardium in a cat model of temporary coronary occlusion and ascertained if replenishment of myocardial phosphate stores during reperfusion as defined by phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy was indicative of salvage. Twenty open chest, anesthetized cats were studied with use of a snare ligature around the proximal left anterior descending coronary artery, with a coil sutured to the epicardial surface overlying the distribution of the artery. Peak areas of phosphocreatine, inorganic phosphate and adenosine triphosphate (ATP) NMR signals were measured during 1 h of occlusion followed by 1.5 h of reperfusion. Infarct size and jeopardy area were determined in vitro by simultaneous infusion of phthalocyanine blue dye and triphenyltetrazolium chloride into the aorta and the left anterior descending coronary artery, respectively, after 5 h of myocardial reperfusion. Nicardipine-treated and control groups had similar jeopardy area values (41.2 +/- 1.6% versus 47.4 +/- 3.1% of the left ventricle), but infarct area was significantly reduced in the nicardipine-treated group (3.2 +/- 1.1% versus 24.9 +/- 7.5% of jeopardy area, p less than 0.01). High energy phosphate compounds remained markedly altered during reperfusion in both groups. No significant improvement in phosphocreatine or inorganic phosphate recovery was observed in animals pretreated with nicardipine despite an 87% reduction in infarct size. Myocardial ATP was greater during reperfusion in the nicardipine-treated compared with the control group (average over initial 90 min of reperfusion 58 +/- 6% versus 46 +/- 3% of baseline values, p less than 0.05), suggesting improved recovery of ATP. However, the measured levels of high energy phosphate compounds during reperfusion and their ratios did not correlate with infarct size and thus were not predictive of myocardial salvage.

Mechanics and energetics of overstretch: The relationship of altered left ventricular volume to the Frank-Starling mechanism and phosphorylation potential

Isovolumic perfused rat hearts containing an intraventricular balloon were used to assess the effects of incremental balloon volumes on developed pressure, oxygen consumption, coronary flow, phosphorylation potential obtained by P-31 nuclear magnetic resonance, wall thickness obtained by two-dimensional echocardiography, and diastolic wall stress. Three phases in developed pressure were noted: (1) volumes from 0 to 150 microliter resulted in a continuous increase in developed pressure; (2) with volumes from 150 to 250 microliter, developed pressure remained constant whereas developed (systolic) and diastolic wall stress rose sharply; and (3) with volumes from 250 to 400 microliter, developed pressure fell whereas developed (systolic) and diastolic wall stress continued to rise. The ln [(PCr)/(Pi)] was in synchrony with oxygen consumption at 0 and 50 microliter balloon volumes, and then diverged at volumes greater than 100 microliter. Oxygen consumption increased from 0 to 50 microliter, was constant from 50 to 250 microliter balloon volume, and then declined. The ln [(PCr)/(Pi)] fell precipitously at balloon volumes greater than 100 microliter, most likely limited by oxygen consumption. Coronary flow did not change significantly until 250 microliter or more of water was added to the balloon, and then it started to decline. Volumes greater than 100 microliter result in overstretch of myofibers, as observed by the precipitous decline in ln [(PCr)/(Pi)], and the steep increase in diastolic wall stress. With excessive volume loading, the drop in phosphorylation potential, ln [(PCr)/(Pi)], appears to contribute to the decrease in developed pressure.

Mechanism for depressed cardiac function in left ventricular volume overload

To assess the effects of left ventricular chamber volume on the mechanism of changes in left ventricular developed pressure we performed phosphorous-31 nuclear magnetic resonance spectroscopy, hydrogen-1 nuclear magnetic resonance spectroscopy with a shift reagent, two-dimensional echocardiography, atomic absorption spectrophotometry, microsphere analysis, and surface fluorometry on isovolumic isolated perfused rat hearts with incremental intraventricular balloon volumes, while left ventricular pressure was concurrently monitored. A three-phasic response of developed pressure was noted: 0 to 100 microliters balloon volumes resulted in an increase in developed pressure, whereas developed pressure remained constant at 250 microliters and fell at 400 microliters. Oxygen consumption and [Ca2+]i transients followed the same pattern as developed pressure and coronary flow. Intraventricular volumes of 250 microliters or greater (a volume overload) caused endocardial ischemia, a greater decrease in extracellular versus intracellular water, thinning of the left ventricular free wall, and an increase in chamber size. Mechanical pressure on the tissue, induced by the volume overload, caused ischemia as further evidenced by (1) a negative effect on developed pressure, (2) a decrease in [Ca2+]i transients, (3) a [Ca2+]i overload, (4) a moderate decrease in the phosphorylation potential, and (5) an increase in the oxidation-reduction state (nicotinamide-adenine dinucleotide). The high intracellular calcium associated with volume overload may have been due to both compression and ischemia, which leads to an increased number of cross-bridges in rigor, a high end-diastolic pressure, and an increase in wall stress.