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R Krams

Publications and source records attributed to R Krams.

50 records · Page 3Linked to original sources
PubMed1993

Altered coronary flow reserve in the hypertrophied heart: implications for therapy.

Coronary flow reserve has been shown to be abnormally low in several models of left ventricular hypertrophy induced by long-standing pressure overload. Because the presence of hypertrophy is a risk factor for the development of subendocardial ischaemia and sudden death, efforts to restore alterations in flow reserve may prove beneficial. In the following review, we discuss potential mechanisms which might contribute to this abnormal vasodilator capacity in the hypertrophied heart, with particular emphasis on how chronic therapy may potentially reverse such abnormalities. In addition, we report how the acute administration of various classes of pharmacological agents can alter measurements of coronary flow reserve, as observed in our anaesthetised swine model. Such factors must be considered before interpreting any changes in coronary flow reserve in models of hypertrophy following chronic administration of drugs.

Animals↗
PubMed1992

L-propionylcarnitine and myocardial performance in stunned porcine myocardium.

Recently, we showed that L-propionylcarnitine did not affect recovery of regional contractile function of porcine myocardium subjected to 1 h of low-flow ischemia followed by 2 hr of reperfusion. In that study, ischemia may have been too severe and/or the duration of reperfusion too short to detect a beneficial effect of the compound. Therefore, in the present study we investigated the effects of saline (control group; n = 14) or pretreatment with L-propionyl-carnitine (3 days of 50 mg/kg p.o. b.i.d. + 50 mg/kg i.v. prior to the experiment; n = 13) on recovery of regional contractile function of the myocardium in open-chest anesthetized pigs, subjected to two cycles of 10 min of left anterior descending coronary artery (LADCA) occlusion, each followed by 30 min of reperfusion. In the control animals, at the end of the second reperfusion period, systemic vascular resistance had increased by 18%, which, however, was not observed in the L-propionylcarnitine-treated pigs. In the control group, during the first occlusion, systolic segment length shortening (SSLS) of the LADCA-perfused area decreased from 18.5 +/- 5.5% to -3.7 = 3.2%. After 30 min of reperfusion, SSLS of the LADCA-perfused area had only partially recovered to 6.2 +/- 5.9%. During the second occlusion-reperfusion cycle similar values for SSLS were observed. In the treated animals, SSLS of the LADCA-perfused area was slightly improved after the second occlusion-reperfusion cycle (p = 0.056). This effect did not result in an overall improvement in cardiac pump function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Pressure-maximal coronary flow relationship in regionally stunned porcine myocardium.

In view of variable results on maximal coronary blood flow in stunned myocardium, we studied the pressure-maximal coronary flow (PMCF) relationship in stunned myocardium in 12 anesthetized swine by using intracoronary adenosine (20 micrograms/kg). Subendocardial systolic segment shortening (SS) measured with sonomicrometry was 19 +/- 5% (means +/- SD) at baseline and 7 +/- 6% (P less than 0.01) at 30 min of reperfusion after 15 min of low-flow ischemia, at which time postsystolic shortening was present. Myocardial stunning increased the slope of the PMCF regression line (alpha PMCF) from 3.34 +/- 1.03 to 3.89 +/- 1.33 ml.min-1.mmHg-1 (P less than 0.01). Atrial pacing at 40 beats/min above spontaneous heart rate (n = 6) further reduced subendocardial SS to 6 +/- 6% (P less than 0.05). Dobutamine (4 micrograms.kg-1.min-1; n = 6) increased subendocardial SS to 13 +/- 5% (P less than 0.05) and abolished postsystolic shortening. Both interventions left alpha PMCF unchanged. In conclusion, myocardial stunning was associated with an increase in alpha PMCF that most likely resulted from the decreased contractile function. The absence of an effect of dobutamine may be due to its predominant action on diastolic function.

Animals↗
PubMed1992

Recruitment of myocardial work and metabolism in regionally stunned porcine myocardium.

We characterized postischemic changes in myocardial metabolism and regional external work, as measured by the integral of left ventricular pressure-segment-length loops. In 12 anesthetized swine, the left anterior descending coronary artery (LAD) was occluded for 10 min and reperfused for 30 min for two successive cycles. Before ischemia, regional work was 16,920 +/- 5,630 mmHg-mm/min and after stunning, work was reduced to 50 +/- 14% (P < 0.05). At baseline, oxygen and lactate consumption were 4.80 +/- 1.40 and 1.02 +/- 0.46 mumol.min-1 x g-1, respectively, and after stunning they were reduced to 3.24 +/- 0.80 (P < 0.05) and 0.16 +/- 0.21 mumol.min-1 x g-1 (P < 0.05), respectively. The atria were then paced 50 beats/min higher than the reperfusion heart rate, during and without an infusion of dobutamine (2 micrograms.kg-1 x min-1). During dobutamine, both regional external work and oxygen consumption returned to 98% of preischemic values, but lactate utilization remained depressed. We conclude that regional external work and oxygen consumption remain coupled during inotropic stimulation after stunning, with a preferential shift toward nonlactate substrates.

Animals↗
PubMed1991

Does intravenous milrinone have a direct effect on diastolic function?

Bipyridine derivatives have recently been introduced as a new class of inodilator drugs in the intravenous therapy of heart failure. A member of this class is milrinone, which improves the inotropic state and reduces ventricular afterload, leading to improved hemodynamics. Because systolic and diastolic function are intimately related, it can be expected that the diastolic muscle properties are influenced by changes in systolic function and therefore by milrinone therapy. Since end-diastolic pressure may shift as a result of a change in ventricular volume alone, a complete left ventricular diastolic pressure volume (LVDPV) relationship must always be measured before one can make firm conclusions regarding changes in diastolic function. After a LVDPV relationship is obtained, one should identify the variables that can modify this relationship without directly affecting the intrinsic diastolic muscle properties. These variables can be divided into static effects (coronary vascular bed volume, right ventricular pressure, and pericardial pressure) and dynamic effects (viscoelasticity and myocardial active relaxation). Increments in coronary perfusion pressure of perfusion flow (vascular bed volume) are known to stiffen the cardiac wall (turgor effect). Changes in right ventricular pressure or pericardial pressure are other factors affecting the LVDPV relationship by changing transmural pressure. This effect is more pronounced when the ventricle is already stiff, such as in patients with myocardial hypertrophy. Dynamic effects become important when a LVDPV relationship is measured during isolated cardiac cycles; they include viscoelasticity and abnormal myocardial relaxation. Clinical assessment of diastolic cardiac performance assumes a model in which the heart is considered an elastic body (while in fact it is viscoelastic).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiotonic Agents↗
PubMed1991

Endothelium dependent vasodilatation following brief ischaemia and reperfusion in anaesthetised swine.

STUDY OBJECTIVE: The aim as to compare the responses of intracoronary infusions of ATP, an endothelium dependent vasodilator, with adenosine following brief ischaemia (10 min) and reperfusion in a model of myocardial stunning. DESIGN: In group 1 (n = 6), coronary blood flow and endocardial (endo) and epicardial (epi) percent segment length shortening were measured in the distribution of the left anterior descending coronary artery before and during maximal intracoronary infusions of either adenosine or ATP (20 micrograms.kg-1.min-1). Measurements were obtained before and after myocardial stunning both at control heart rate and during atrial pacing (150 beats.min-1). In group 2 (n = 6), myocardial blood flows by microspheres and arterial-venous lactate and oxygen differences were determined following the same ischaemia-reperfusion protocol to characterise transmural changes in blood flow and metabolism in this model of stunning. EXPERIMENTAL MATERIAL: The experiments were done on 12 anaesthetised swine, weight 25-39 kg. MEASUREMENTS AND MAIN RESULTS: In group 1, baseline endo and epi segment length shortening were 16(SD 3)% and 14(6)% and following reperfusion were reduced to 10(4)% and 8(6)% respectively (p less than 0.05). Prior to stunning, minimal coronary resistances during adenosine and ATP were 0.81(0.40) and 0.76(0.25) mm Hg.min.ml-1 respectively and following reperfusion were 0.86(0.31) (NS) and 0.85(0.23) (NS) mm Hg.min.ml-1 respectively. Infusion of either vasodilator enhanced function by 30% following reperfusion whereas no such effect was observed prior to ischaemia. In group 2, no maldistribution of blood flow was observed following the same ischaemia-reperfusion protocol to account for this vasodilator enhancement in function. Percent lactate extraction values were 29(11)% and 25(14)% at preischaemic control and paced heart rates respectively, and following reperfusion were lowered to 0(12)% without pacing (p less than 0.05) and -1(34)% during pacing (p less than 0.05). CONCLUSIONS: Brief ischaemia and reperfusion in swine induces myocardial stunning without altering the vasodilator responses of either ATP, an endothelium dependent vasodilator, or adenosine. Recruitment in postischaemic segment length shortening was observed during infusions of both vasodilators at a time when maldistribution of flow was not observed. Possible mechanisms include either enhanced washout of lactate from the reperfused myocardium or greater utilisation of substrates during higher blood flows.

Adenosine↗
PubMed1990

Coronary oscillatory flow amplitude is more affected by perfusion pressure than ventricular pressure.

In this study on the isolated, maximally vasodilated, blood-perfused cat heart we investigated the relation between left ventricular developed pressure (delta Piv) and coronary oscillatory flow amplitude (diastolic minus systolic flow, delta F) at different levels of constant perfusion pressure (Pp). We hypothesized that the effect of cardiac contraction on the phasic flow results from the changing elastic properties of cardiac muscle. The coronary vessel compartment can, as can the left ventricular lumen compartment, be described by a time-varying elastance. This concept predicts that the effect of left ventricular pressure on delta F is small, whereas the effect of Pp is considerable. Both the waterfall model and the intramyocardial pump model predict the inverse. The relation between delta Piv and delta F at a Pp of 10 kPa is delta F = (4.71 +/- 3.08).delta Piv + 337 +/- 75 (slope in ml.min-1.100 g-1.kPa-1 and intercept in ml.min-1.100 g-1; n = 7); the relation between (constant levels of) Pp and delta F at a constant delta Piv of 10 kPa is delta F = 51.Pp + 211 (slope in ml.min-1.100 g-1.kPa-1 and intercept in ml.min-1.100 g-1; n = 6). The differences in slope are best predicted by the time-varying elastance concept.

Animals↗
PubMed1990

Effect of wall stretch on coronary hemodynamics in isolated canine interventricular septum.

The effects of stretch on coronary pressure-flow relations are not well understood. To examine the role of wall stretch per se on coronary hemodynamics, we studied arterially perfused isolated canine interventricular septa in a noncontracting state with vasodilated vessels. We compared the hemodynamic parameters of zero-flow pressure and resistance during passive stretching in the circumferential and the base-to-apex directions alone as well as during simultaneous biaxial stretching in both directions. Even in the unloaded state the zero-flow pressure was positive. Any type of stretching significantly increased the zero-flow pressure and the resistance from their unloaded values. The pressure-flow responses also showed directional dependence. When stretches with matched strains or stresses in each direction were applied sequentially, the resistance increases corresponded to the direction of higher stress. Conversely, the zero-flow pressure response increase corresponded to the direction of greater strain. However, neither response correlated with a measure of global tissue stiffness. Thus there is a complex and tight mechanical interaction between the vessels and the surrounding tissue. These interactions, but not the tissue stiffness, are important determinants of coronary pressure-flow responses during stretch.

Animals↗
PubMed1989

Varying elastance concept may explain coronary systolic flow impediment.

We measured phasic arterial coronary inflow in the blood-perfused isolated cat heart (n = 5) with a balloon in the left ventricle under well-defined conditions, i.e., constant perfusion pressure, constant vasomotor tone (maximal vasodilation), and heart rate. The normalized amplitude (A) between systolic flow (Fs) and diastolic flow (Fd) [A = (Fd - Fs)/Fd] was related to systolic left ventricular pressure (Ps, range 1.6-17 kPa, 1 kPa = 7.5 mmHg) for different isovolumic beats obtained by changes in balloon volume and for low load isobarically ejecting beats (pressure 0.2 kPa). The data were fitted to A = a + bPs with a = 0.70 +/- 0.15 (SD) and b = 0.005 +/- 0.005 kPa-1. This relation indicates a very weak effect of left ventricular systolic pressure on normalized flow amplitude. Thus the hypothesis that left ventricular pressure is the sole determinant impeding coronary flow could not be confirmed. However, our data could be explained on basis of the time-varying elastance concept (H. Suga, K. Sagawa, and A. A. Shoukas. Circ. Res. 32: 314-322, 1973). The intravascular and luminal (cavity) compartments both are assumed to be subject to a time-varying elastance. The time-varying luminal elastance is similar for isovolumic and isobaric beats. We assume that the elastance of the vascular compartment also behaves the same for these beats, and therefore coronary flow is affected similarly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Contractility is the main determinant of coronary systolic flow impediment.

We measured the relation between coronary flow amplitude (delta F = Fd-Fs; where d is diastolic and s is systolic) and developed left ventricular pressure (delta PLV = Ps-Pd) at a constant perfusion pressure of 75 mmHg (10 kPa) in the maximally vasodilated blood-perfused isolated cat heart for different steady-state levels of contractility (protocol A) and during transients in contractility (protocol B). Contractility was defined as the slope of the end-systolic pressure-volume relation (Emax). From protocol A it appeared that the coronary flow amplitude was only weakly related to left ventricular pressure at each steady-state level of contractility studied. However, the coronary flow amplitude was strongly related to the different levels of contractility. In protocol B, contractility was changed over a wide range of values (0-100%) but developed pressure and contractility changed simultaneously. Using multiple linear regression analysis, we found that contractility has approximately 10 times (range: 2.8-57.3) stronger effect than left ventricular pressure on coronary flow amplitude (n = 10 experiments). These data and our earlier observations suggest that it is the difference in stiffness of cardiac muscle between systole and diastole that determines coronary flow amplitude.

Animals↗
PubMed1988

Changes in coronary pressure-flow relation after transition from blood to Tyrode perfusion.

In six isolated, diastolic-arrested, maximally vasodilated cat hearts, we studied changes in coronary pressure-flow relations (zero-flow pressure intercept, resistance) during the first 25 min, after a change of perfusate, from blood to Tyrode. The apparent intercept (zero-flow) pressure changed from 2.0 +/- 0.94 (+/- SD) kPa during blood perfusion to 2.5 +/- 0.55, 2.6 +/- 0.68, 2.5 +/- 0.94, and 2.7 +/- 1.34 kPa during Tyrode perfusion for 2:15, 5:30, 10:30, and 25:00 min, respectively. Intercept pressures during Tyrode perfusion were significantly different from the intercept pressure during blood perfusion, except for the one measured after 25 min of Tyrode perfusion (P less than 0.05). Resistance (defined as the ratio of perfusion pressure and flow at 10 kPa perfusion pressure) steadily rose to approximately 170% of the value during blood perfusion. The observation that the apparent intercept pressure is maintained, when a particle-free (Newtonian) isotonic perfusate is used, may indicate that this intercept is not a result of blood rheology alone. The increase rather than decrease in resistance suggests an effect of edema, which increases interstitial volume at the expense of intravascular volume.

Animals↗
PubMedDate not supplied

Can coronary systolic-diastolic flow differences be predicted by left ventricular pressure or time-varying intramyocardial elastance?

In six isolated rabbit hearts perfused with a pressure source and Krebs-Henseleit as the perfusion medium, the effect of left ventricular pressure on coronary inflow in the maximally vasodilated bed was studied. This effect was determined from isovolumic beats, low afterloaded isobaric beats (afterload maintained at values below 10 mm Hg) and during cardiac arrest. For isovolumic beats end-diastolic left ventricular pressure was varied by means of an intraventricular balloon between 0-40 mm Hg and systolic left ventricular pressure varied between 90-130 mm Hg. In these ranges diastolic inflow decreased significantly 18 +/- 6% (mean +/- SD) with increasing pressure and systolic inflow could not be shown to depend on pressure (n = 6). For isobaric beats, diastolic and systolic inflow remained at values similar to those found for the isovolumic beats (n = 6). In the arrested heart inflow diminished 8 +/- 2% when the pressure in the left ventricle was increased from 0 to 40 mm Hg (n = 3). We conclude that systolic coronary inflow is hardly affected by left ventricular pressure. Systolic inflow decreased by the same amount in the isovolumically and isobarically beating heart, when cardiac contractility was enhanced by epinephrine infusion. We suggest the results can be explained on the basis of the time-varying elastance concept: systolic elastance is the same for isovolumic and isobaric beats but depends on contractility. Models that relate coronary inflow impediment to left ventricular pressure should therefore be reevaluated.

Animals↗