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Biomedical subjects

I Mirsky

Publications and source records attributed to I Mirsky.

At least 37 records · Page 2Linked to original sources
PubMed1989

Effects of chronic sodium depletion on function of isolated normal and hypertensive hypertrophied rat heart.

Since in vivo ejection fraction is said to be reduced in chronically sodium depleted dogs, this study was conducted to investigate the direct effects of sodium deprivation on intrinsic ventricular contractility, independent of haemodynamic or adrenergic influences. Since low sodium diet and/or diuretics are commonly used in the treatment of hypertension, we included a hypertensive group in the study. Normotensive male Sprague-Dawley rats and age matched renovascular hypertensive rats were subdivided into three groups. The first group was fed regular sodium diet (RS) for 6 weeks. The second (LS) and third (LSD) groups received low sodium diet for 6 weeks, and the LSD group also received diuretic (frusemide) treatment to achieve marked sodium depletion (last dose given 2 weeks before the cardiac study). Left ventricular (LV) contractility was investigated in the isolated isovolumetric rat heart (Langendorff preparation) paced at 180 beats-min-1. Results showed that LV +dP/dt max at zero LV end diastolic pressure was higher (p less than 0.01) in the LSD group than in the other groups in normotensive rats [2672 (SEM127) mm Hg.s-1 in LSD, 2267(96) in LS, 2174(111) in RS] and higher in LSD (p less than 0.01) and LS (p less than 0.05) groups than in the RS group in hypertensive rats [2332(110) mm Hg.s-1, 2287(93), 1781(104), respectively]. Calculated LV balloon volume at zero LV end diastolic pressure was not significantly different in any dietary group. These results suggested that after 6 weeks of in vivo sodium depletion, in vitro LV contractility was enhanced rather than depressed under these experimental conditions. This enhancement is contrary to the in vivo findings in the dog model and could not be explained by differences in myocardial flow rate, LV chamber stiffness or myocardial stiffness constant. The mechanism of this accentuated ventricular contractility under these experimental conditions remains to be determined.

Animals↗
PubMed1988

Left ventricular systolic and diastolic function during acute coronary artery balloon occlusion in humans.

Left ventricular function during percutaneous transluminal coronary angioplasty was studied in 16 patients undergoing the procedure. All measurements were performed before and during the first episode of balloon coronary occlusion. In 16 patients (Group A), data were recorded before and 30 or 50 s after balloon inflation, and in 8 of these patients (Group B) data were also recorded 15 min after the complete procedure. Left ventriculograms indicated a marked dyskinesia of the anterior and apical wall in all patients. After balloon inflation, there was a marked depression in stroke index and ejection fraction and an increase in left ventricular end-diastolic pressure and the time constants of relaxation in all patients. Simultaneous recording of left ventricular pressure (Millar micromanometer) during cineangiography permitted the assessment of myocardial and chamber stiffness. Although there was a strong tendency for both myocardial and chamber stiffness to increase after 30 to 50 s of occlusion, these increases were statistically insignificant. In Group B, a third set of angiographic and pressure measurements obtained 15 min after completion of the coronary angioplasty procedure indicated no residual left ventricular dysfunction, and in this respect, the results are of added clinical importance.

Angioplasty, Balloon↗
PubMed1988

Sympathetic augmentation of cardiac function in developing hypertension in conscious dogs.

To determine the alterations in left ventricular (LV) function and the mechanisms involved that occur during the development of perinephritic hypertension, dogs were instrumented with a miniature LV pressure transducer, aortic and left atrial catheters, and ultrasonic crystals to measure LV diameter in the short and long axes and wall thickness. At 2 wk after initiation of perinephritic hypertension, increases (P less than 0.05) were observed in LV systolic pressure, LV end-diastolic pressure, both short- and long-axis end-diastolic diameters, calculated LV end-diastolic volume, stroke volume, global average LV systolic wall stress, first derivative of LV pressure (LV dP/dt), and ejection fraction, whereas mean velocity of circumferential fiber shortening (Vcf) and rate of change of LV short-axis diameter (LV dD/dt) rose but not significantly. At three levels of matched preload and afterload induced by the administration of graded doses of phenylephrine, Vcf, LV dD/dt, and LV dP/dt increased in hypertension compared with the same levels of preload and afterload before hypertension. When the loading conditions in the normotensive and hypertensive dogs were matched, either after ganglionic blockade or beta-adrenergic blockade, both isovolumic and ejection-phase indexes of LV function remained similar before and after hypertension. Thus we conclude that 1) LV function in intact, conscious dogs with early hypertension is enhanced, and 2) the major mechanism for the increase in LV function involves the sympathetic nervous system.

Animals↗
PubMed1988

Correction for preload in assessment of myocardial contractility in aortic and mitral valve disease. Application of the concept of systolic myocardial stiffness.

With single-beat analysis, the new concept of systolic myocardial stiffness is applied to provide a new approach for the assessment of myocardial contractility in aortic and mitral valve disease. Seventy patients underwent diagnostic right and left heart catheterization. Twenty-six patients had aortic stenosis, 18 had aortic insufficiency, and 26 had mitral regurgitation. Patients with aortic stenosis were divided into two groups on the basis of left ventricular mass index less than 172 g/m2 (AS1) and mass index greater than or equal to 172 g/m2 (AS2). The mitral regurgitation patients were divided into those in normal sinus rhythm (MR1) and those in atrial fibrillation (MR2). Nine patients without significant coronary or cardiovascular disease served as controls. Thirteen patients with aortic stenosis and eight with aortic insufficiency were evaluated (average, approximately 18 months) after successful aortic valve replacement. With simultaneous left ventricular pressure and cineangiographic methods, myocardial contractility was assessed by the conventional ejection fraction-afterload relation (uncorrected for preload) and by two new methods that permit the correction of the ejection fraction for preload. Assessments of the contractile state by these two new methods differed from those by the conventional method in 20-40% of the cases studied. Contractile state improved postoperatively in aortic stenosis and aortic insufficiency even in patients with preoperative depressed contractile states. In patients with mitral regurgitation, there was considerable heterogeneity of contractile function preoperatively. Severe left ventricular hypertrophy in aortic stenosis was not a marker for postoperative outcome since contractility was normal postoperatively in AS1 and AS2 in equal numbers. This study demonstrates that preload correction is important in a preoperative assessment of contractility in aortic and mitral valve disease but that it is less important postoperatively, presumably because of reductions in the preload.

Adult↗
PubMed1988

Systolic and diastolic dysfunction during atrial pacing in conscious dogs with left ventricular hypertrophy.

To determine the extent to which the hypertrophied left ventricle responds to the chronotropic stress induced by graded atrial pacing rates, we studied conscious, chronically instrumented dogs with severe compensated pressure overload left ventricular (LV) hypertrophy induced by aortic banding in puppies 8-10 weeks of age. At 1-2 years, dogs with severe LV hypertrophy (LV free wall/body wt ratio 6.8 +/- 0.6 g/kg) and sham-operated littermates (LV free wall/body wt ratio 4.0 +/- 0.3 g/kg) were instrumented with ultrasonic dimension crystals to measure LV short axis internal diameter and wall thickness, miniature LV pressure transducers, and aortic and LV catheters. During atrial pacing (240 beats/min) in eight control dogs, LV pressure did not change from 119 +/- 2 mm Hg, and mean velocity of circumferential fiber shortening (VCF) did not change from 1.25 +/- 0.09/sec. In seven dogs with LV hypertrophy, atrial pacing (240 beats/min) decreased systolic LV function; that is, LV systolic pressure decreased (p less than 0.01) by 65 +/- 12 from 254 +/- 14 mm Hg, and VCF decreased (p less than 0.01) by 0.19 +/- 0.03 from 0.97 +/- 0.15/sec. Diastolic dysfunction was also observed in the dogs with LV hypertrophy. In the control dogs during atrial pacing (240 beats/min), LV end-diastolic pressure decreased (p less than 0.01) by 8 +/- 1 from 9 +/- 1 mm Hg, end-diastolic stress decreased (p less than 0.01) by 18 +/- 2 from 22 +/- 2 g/cm2, and the radial myocardial stiffness constant did not change from 5.6 +/- 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Effects of myocardial ischemia on regional function and stiffness in conscious dogs.

The extent to which cardiac nerves influence responses of regional ventricular function to acute myocardial ischemia was investigated in conscious dogs with intact cardiac innervation (N) and dogs with chronic cardiac denervation (D). Following coronary artery occlusion (CAO) left ventricular (LV) end-diastolic pressure increased more (P less than 0.01) in D (18 +/- 3.2 mmHg) than in N dogs (3.4 +/- 0.7 mmHg), whereas heart rate increased more in N (32 +/- 4.8 beats/min) than in D dogs (16 +/- 3.0 beats/min). In nonischemic zones of D dogs there were greater increases, P less than 0.05, in end-diastolic segment length, systolic segment shortening, and velocity of shortening than in N dogs. In ischemic zones, significantly greater increases in end-diastolic segment length were also observed in the D group, but similar reductions in segmental shortening occurred in both N (-116 +/- 2.8%) and D (-108 +/- 5.2%) dogs. The time constant of isovolumic relaxation was not different in the two groups. However, in ischemic zones of N dogs myocardial stiffness constant (k) increased by 109 +/- 24 from 33 +/- 4.9 and end-diastolic stiffness (Eed) rose by 1527 +/- 310 from 253 +/- 34 mmHg, whereas k increased significantly less (P less than 0.05) in D dogs. Eed of ischemic zones also rose significantly less (P less than 0.05) in D dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The development of the entire end-systolic pressure-volume and ejection fraction-afterload relations: a new concept of systolic myocardial stiffness.

In this study we introduce a new concept of systolic myocardial stiffness that extends the Suga-Sagawa maximum ventricular elastance concept to the myocardium. End-systole is defined as the time of maximum systolic myocardial stiffness (max Eav), which we examined for its load independence and sensitivity to changes in the inotropic state and to heart rate. Seven adult mongrel dogs were instrumented with ultrasonic crystals for measurements of long and short axes and left ventricular wall thickness, and a high-fidelity micromanometer was inserted for measurement of left ventricular pressures. Preload and afterload were altered by inferior vena cava occlusion, nitroprusside, angiotensin II, atropine, propranolol, and various combinations with propranolol. End-systolic stress-strain relations (slope: max Eav) were linear in all seven dogs, implying that end-systolic myocardial stiffness is independent of end-systolic stress. Changes in max Eav (for constant preload and afterload) reflected changes in the ejection fraction; max Eav was also insensitive to propranolol and to changes in heart rate over the range from 120 to 180 beats/min. End-systolic pressure-volume relations (ESPVRs), derived analytically from these stress-strain relations, were nonlinear, and estimates of volume at zero stress (Vom) were always positive. On the other hand, ESPVRs obtained on the basis of the Suga-Sagawa maximum ventricular elastance concept, were linear, and volume at zero pressure (Vop) estimated by linear extrapolation was negative in one case. Based on the concept of systolic myocardial stiffness, the slope of the ESPVR varies with end-systolic volume and attains its maximum value (Emax) at zero end-systolic pressure. Normalization of Emax with Vom demonstrated a close relationship to max Eav. Thus both max Eav and Vom and Emax are ideal variables for assessing changes in myocardial contractility when preload and afterload are constant. Furthermore, Vom and max Eav permit development of the entire ejection fraction-afterload relationship for a given preload, thus providing a method for comparing myocardial contractile states between ventricles.

Animals↗
PubMed1986

Mechanical and inotropic reserve in conscious dogs with left ventricular hypertrophy.

We studied the left ventricular (LV) responses to infusions of norepinephrine and prenalterol, a specific beta 1-adrenergic receptor agonist, in conscious, chronically instrumented adult dogs with severe LV hypertrophy. The goal of this study was to determine the extent of compensation induced by LV hypertrophy in an animal model in which the pressure overload was gradually increased, as occurs in human pathological states. One to 2 yr after banding the ascending aorta of puppies, six dogs with severe LV hypertrophy (LV free-wall weight-to-body weight ratio 7.0 +/- 0.4 g/kg), and nine sham-operated littermates (LV free-wall weight-to-body weight ratio 4.0 +/- 0.2 g/kg) were studied. The dogs were instrumented with ultrasonic dimension crystals (to measure LV short-axis diameter and wall thickness), miniature LV pressure transducers, and LV and aortic catheters. In the control dogs norepinephrine (0.4 micrograms X kg-1 X min-1) increased LV systolic/diastolic pressure from 121 +/- 2/9 +/- 1 to 177 +/- 9/20 +/- 2 mmHg, mean arterial pressure from 97 +/- 2 to 143 +/- 9 mmHg, LV dP/dt from 3,363 +/- 123 to 5,174 +/- 343 mmHg/s, and mean systolic wall stress from 194 +/- 14 to 299 +/- 22 g/cm2, while mean velocity of circumferential fiber shortening (Vcf), (dD/dt/D)max, and heart rate did not change from base line. In dogs with LV hypertrophy norepinephrine increased LV pressure from 224 +/- 16/11 +/- 1 to 305 +/- 22/19 +/- 1 mmHg, mean arterial pressure from 90 +/- 2 to 132 +/- 4 mmHg, LV dP/dt from 3,246 +/- 156 to 5,619 +/- 345 mmHg/s, and mean systolic wall stress from 224 +/- 11 to 307 +/- 24 g/cm2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Myocardial relaxation and passive diastolic properties in man.

We have developed a model for assessing the influence of the decaying contractile systolic tension on diastolic wall dynamics and the passive properties of left ventricular muscle. Total measured left ventricular diastolic pressure and stress (sigma T) are determined by two overlapping processes: the decay of actively developed pressure and stress (sigma A) and the buildup of passive filling pressure and stress (sigma*). The decaying contractile stress sigma A is formulated in terms of a relaxation pressure with a time constant (T) assessed during the isovolumic relaxation interval. By subtracting the contribution of sigma A from sigma T we obtain sigma*. With micromanometry, echocardiography, and cineangiography, total and passive stress-strain relations and strain rates were evaluated over the entire filling period in six normal control subjects and in seven patients with aortic stenosis. Elastic stiffness constants (k), the slopes of the linear passive stiffness vs sigma* relations, did not differ in the two groups over a common lower stress range (6/6 normal, k = 9.37 +/- 1.23; 7/7 aortic stenosis, k = 9.34 +/- 1.08). Over a higher sigma* range, transition into a much steeper linear region occurred, and k values were much larger (4/7 aortic stenosis, k = 28.76 +/- 2.02). When diastolic stress levels are elevated, passive stiffness-stress relations can be better described as bilinear, with a much greater wall stiffness constant in the higher than in the lower stress range. Dynamic effects of decaying systolic contractile wall stress components are important in the rapid filling phase in normal hearts as well as in those with aortic stenosis.

Angiocardiography↗
PubMed1985

Different effects of two types of ischemia on myocardial systolic and diastolic function.

Acute increases in left ventricular (LV) diastolic pressure relative to volume occur during angina in humans and after pacing tachycardia in dogs with coronary stenoses. In this study we assessed myocardial function following pacing tachycardia in dogs with coronary stenoses and compared it with function of the same myocardial segment during coronary occlusion. Also we calculated regional wall stiffness following pacing tachycardia in dogs with coronary stenoses. In anesthetized dogs with two-vessel critical (90%) coronary stenoses, ultrasonic crystals were implanted subendocardially to measure either anterior wall (AW) and lateral wall (LW) segment lengths (SL; n = 14) or LV wall thickness (h; n = 7). LV pressure was measured using a high-fidelity micromanometer catheter. After pacing tachycardia in dogs with two-vessel coronary stenoses, there was a substantial rise in LV end-diastolic pressure (from 6 +/- 1 to 15 +/- 1 mmHg; P less than 0.001), a slight increase in end-diastolic segment length (AWEDSL from 15.6 +/- 1.0 to 16.4 +/- 1.0 mm; p less than 0.01; and LWEDSL from 13.8 +/- 1.4 to 14.3 +/- 1.4 mm; P greater than 0.01) and a reduction of percent systolic shortening of the ischemic segments. An upward shift of the diastolic pressure-SL relation was observed in the postpacing period. During coronary occlusion the diastolic pressure-SL relation of the same segment shifted rightward, or rightward and downward, and systolic shortening became holosystolic bulging. Ischemia due to coronary stenoses plus increased O2 demand had substantially different effects on regional wall motion and segmental diastolic mechanics than did ischemia due to coronary occlusion. Over the same range of residual transmural LV diastolic pressure, the radial stiffness modulus was higher after pacing tachycardia in the presence of coronary stenoses.

Animals↗
PubMed1984

Measurement of arterial pressure-dimension relationships in conscious animals.

Currently, considerable clinical interest exists in the vasoactivity of large coronary arteries due to the prevalence of coronary vasospasm in mediating angina pectoris and even myocardial infarction. Although arterial elastic properties have been studied extensively in acute, anesthetized animal experiments and in vitro preparations, few data are available on these properties in conscious, chronically instrumented animals, where the complicating influences of anesthesia, recent surgery, and acute manipulation of the vessel are minimized. To study vascular smooth muscle in the conscious animal we modified the transit-time dimension measurement technique by designing smaller, higher frequency (7 MHz) transducers, and introducing electronic refinements to accurately measure smaller dimensions (2 mm minimum). We applied this technique to the left circumflex coronary (LCC) artery, along with arterial pressure measurements from either chronically implantable strain-gauge manometers, or microtip catheter manometers, to study dynamic compliance and vascular control mechanisms of these arteries for periods of months in conscious, chronically instrumented animals. Infusion of an alpha-adrenergic vasoconstrictor, methoxamine (50 micrograms/kg/min), caused sustained reduction in LCC diameter (9% +/- 2%) at a time when mean arterial pressure rose by 65% +/- 5% and heart rate and mean coronary blood flow (electromagnetic flow probe) were returned to control levels. Methoxamine induced a marked leftward shift in the pressure-diameter and stress-radius relationships, reducing vascular caliber for any given stress and pressure level. Moreover, smooth-muscle activation raised the effective incremental modulus (Einc) of the coronary arterial wall when compared at similar radii, but it reduced Einc when compared at similar stress or pressure levels. Thus, for any given arterial pressure level the Einc of the LCC artery wall can be reduced considerably by the enhanced smooth-muscle activation elicited by methoxamine. Nitroglycerin (25 micrograms/kg) induced an initial decrease in LCC diameter as pressure fell and LCC blood flow rose. However, dimensions then increased, reaching a maximum 5 minutes later, when LCC blood flow was reduced, and heart rate and left ventricular dP/dt were at control levels. The calcium-channel antagonist, nifedipine, caused similar early changes, with the increase in LCC caliber persisting for 46 +/- 5 minutes while LCC blood flow returned to control in 15 +/- 3 minutes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

Prevention of the development of heart failure and the regression of cardiac hypertrophy by captopril in the spontaneously hypertensive rat.

The spontaneously hypertensive rat (SHR) exhibits both a compensated phase of cardiac hypertrophy in which forward output is maintained despite persistently elevated systemic arterial pressures and a decompensated phase in which cardiac performance has deteriorated in spite of further hypertrophic growth. To determine whether chronic antihypertensive therapy prevents the development of heart failure and the progression of cardiac hypertrophy in SHR with advanced hypertension, captopril (2 g/l of drinking water), a converting enzyme inhibitor, was administered to 14 month old female SHR and normotensive American Wistar rats (NWR) for 10 months. The severe left ventricular hypertrophy of the 24 month old untreated SHR (4.37 +/- 0.2 mg/g v. 2.50 +/- 0.06 mg/g, untreated NWR) was markedly reduced (P less than 0.02) by captopril (3.01 +/- 0.1 mg/g). Chronic therapy prevented the reduction of both baseline and maximal cardiac indices in SHR, but did not alter blood flow in NWR. Left ventricular dilatation was present in 24 month old SHR and, as peak stroke volume index was diminished, the ejection fraction index of the SHR was reduced. Captopril restored this index in SHR to normal. The relation of ejection fraction index and afterload (peak systolic wall stress) was depressed in untreated SHR, but was normal in treated SHR. Thus, chronic therapy with captopril prevented the development of severe cardiac dysfunction and produced a marked regression of cardiac hypertrophy in SHR with advanced hypertensive heart disease.

Age Factors↗
PubMed1983

Increased regional myocardial stiffness of the left ventricle during pacing-induced angina in man.

The left ventricular diastolic pressure-volume relationship shifts upward during angina, but why this happens is not known. To assess regional myocardial stiffness, we studied 12 patients who had coronary artery disease using simultaneous left ventricular micromanometer pressure recording and M-mode echocardiography before and during angina induced by pacing tachycardia. All patients had two- or three-vessel coronary artery disease that involved the posterior left ventricular wall circulation and had positive pacing stress tests, i.e., development of angina and a postpacing rise in left ventricular end-diastolic pressure (15 +/- 3 to 31 +/- 6 mm Hg, p less than 0.001). A marked upward shift in the relationship between the diastolic left ventricular pressure and the posterior wall thickness (h) occurred after pacing tachycardia, but the change in left ventricular posterior wall end-diastolic thickness was minimal (8.9 +/- 2.1 to 9.2 +/- 2.1 mm, NS). After pacing, the peak rate of left ventricular posterior wall thinning decreased (82 +/- 37 to 48 +/- 27 mm/sec, p less than 0.005) and the time constant of relaxation derived from the best exponential fit to the isovolumic left ventricular pressure decay increased (49 +/- 5 to 58 +/- 7 msec, p less than 0.001). Diastolic active left ventricular pressure decay, extrapolated from the exponential fit, was subtracted from the measured left ventricular pressure (which is equal in magnitude but opposite in sign to the radial stress at the endocardium) to calculate residual left ventricular pressure (PR) and hence residual stress (sigma R = -PR). A radial stiffness modulus (ER) was determined by the slope of the PR vs log h plots before and after pacing. Over the same range of residual radial stress (sigma R), ER was always higher during pacing-induced angina, indicating increased residual myocardial stiffness. Increased myocardial stiffness in addition to a decreased rate of wall thinning and slow active pressure decay contribute to the upward shift in left ventricular pressure-wall thickness and pressure-volume relationships during pacing-induced angina.

Adult↗
PubMed1983

The contractile state as the major determinant in the evolution of left ventricular dysfunction in the spontaneously hypertensive rat.

Female spontaneously hypertensive and normotensive rats were studied at 6, 12, 18, and 24 months of age to determine which characteristics of myocardial performance herald the onset of left ventricular dysfunction. Peak ejection fraction index was derived from measurements of peak stroke volume (in vivo volume loading) and passive pressure-volume relations. The myocardial stiffness constant (km, slope of the incremental modulus-stress relation, EINC = km sigma), chamber stiffness constant (kc, slope of the chamber stiffness-pressure relation, dP/dV = kcP), and left ventricular cavitary volume-to-wall volume ratio at 10 mm Hg) were calculated from the pressure-volume data and the contractile state was assessed from the ejection fraction index-afterload relations. In the normotensive rats, the myocardial stiffness constant was not affected by age, whereas, in the spontaneously hypertensive rats, the myocardial stiffness constant remained within normal limits until 18 months, at which time a significant increase in this index of myocardial stiffness occurred. Baseline and maximal cardiac indices and ejection fraction index of spontaneously hypertensive rats were normal from 6 to 18 months, but were markedly reduced at 24 months. This reduction in cardiac performance was associated with a decrease in the left ventricular chamber stiffness constant, i.e., kc. This decreased chamber stiffness, which occurred at a time when myocardial stiffness was increased, was due to a greater increase in cavity size than in myocardial stiffness. The left ventricular cavity-to-wall volume ratio of normotensive rats was not affected by age, whereas, in the spontaneously hypertensive rats, this ratio markedly declined by 18 months. The ejection fraction index-afterload relations i.e., a measure of the contractile state, of the 6- and 12-month-old spontaneously hypertensive rats were similar to those of the normotensive rats of all ages. However, a depression in the contractile state of the spontaneously hypertensive rats occurred at 18 months and was further depressed at 24 months. This abnormality of the contractile state was evident before the deterioration of cardiac performance, as reflected in a decrease in baseline and maximal cardiac indices, and dilation of the left ventricle occurred. The contractile state (ejection fraction index-afterload relation) is thus the most sensitive indicator of left ventricular dysfunction in spontaneously hypertensive rats.

Animals↗
PubMed1982

Regression of left ventricular hypertrophy and prevention of left ventricular dysfunction by captopril in the spontaneously hypertensive rat.

To determine whether chronic antihypertensive therapy prevents the progression of cardiac hypertrophy and the deterioration in cardiac performance observed in spontaneously hypertensive rats (SHR) with long-term hypertension, 14-month-old female SHR and normotensive American Wistar rats (NWR) were treated for 10 months with an inhibitor of angiotensin I-converting enzyme, captopril (2 g/liter of drinking water). Captopril reduced the marked left ventricular hypertrophy of 24-month-old SHR (untreated, 4.37 +/- 0.2 mg/g of body weight; treated, 3.01 +/- 0.1 mg/g; P less than 0.02) to levels observed in 6-month-old SHR. Treatment prevented the reductions in baseline and maximal aortic blood flows that occurred in SHR between ages 12 and 24 months yet had no effect on the blood flows of NWR. The diminished maximal stroke volume of untreated SHR was ejected from a significantly increased left ventricular end-diastolic volume, so that the ejection-fraction index was markedly reduced (24-month-old untreated NWR, 84 +/- 3%; untreated SHR, 56 +/- 5%; P less than 0.001). Therapy restores this index in SHR to normal (77 +/- 4%). The relationship between ejection-fraction index, and afterload was also normal in treated SHR. Thus, chronic therapy with captopril produced a marked regression of cardiac hypertrophy and prevented the deterioration of cardiac performance in SHR with long-standing hypertension.

Age Factors↗
PubMed1982

Diastolic myocardial stiffness in gradually developing left ventricular hypertrophy in dog.

The effects of gradually developing left ventricular pressure overload on diastolic myocardial stiffness were studied in a chronic moderate hypertrophy model. A snug aortic band was placed beneath the left coronary artery in six puppies 4.5 wk of age, and hemodynamic studies were performed 33.5 wk later. In all six dogs, moderate pressure gradients (10-58 mmHg) developed across the constriction, and angiographic area of the aortic constriction was significantly smaller than for a control group, 4.9 +/- 0.5 vs. 8.4 +/- 0.8 mm2/kg, (mean +/- SE, P less than 0.05). Increases occurred in left ventricular (LV) wall thickness (1.08 +/- 0.07 vs. 0.83 +/- 0.04 cm, P less than 0.05), LV wall mass (5.2 +/- 0.3 vs. 4.1 +/- 0.2 g/kg, P less than 0.05), and wall thickness-to-radius ratio (0.67 +/- 0.04 vs. 0.50 +/- 0.03, P less than 0.01), whereas no differences were noted in LV end-diastolic pressure (11 +/- 1 vs. 9 +/- 1 mmHg), LV end-diastolic volume (LVEDV, 2.06 +/- 0.22 vs. 2.35 +/- 0.15 ml/kg) or ejection fraction (71 +/- 4 vs. 71 +/- 3%). The values of LV wall mass, LVEDV, and aortic constriction are normalized to body weight. Diastolic LV myocardial stiffness was examined in terms of the elastic stiffness-stress relations. There were small and insignificant differences in end-diastolic stress (17.3 +/- 1.5 vs. 20.4 +/- 3.8 g/cm2), myocardial stiffness constant (Km, 13.7 +/- 5.6 vs. 11.2 +/- 3.3), and end-diastolic elastic stiffness (221 +/- 67 vs. 221 +/- 79 g/cm2) between hypertrophied and control hearts. No significant differences in the elastic stiffness of hypertrophied and normal muscle were observed over the common stress range of 5-25 g/cm2. We conclude that moderate left ventricular hypertrophy in chronic, gradually developing pressure overload is an adaptation process associated with normal myocardial stiffness.

Animals↗