Biomedical subjects
Publications and source records attributed to R H Helfant.
This report presents an overview of the problem of treating congestive heart failure. Emphasis is on the arrhythmia component and the complex interrelationships of critical electrolytes and pathophysiologic factors that can lead to sudden cardiac death.
Tumor necrosis factor (TNF) is a secretory product of normal macrophages that can cause cell necrosis, new blood vessel formation and thrombosis. These are also 3 characteristic features of the progression of stable atheroma to endothelial disruption. Accordingly, an immunohistochemical method was developed to detect TNF in human tissue. Using this method TNF positivity was demonstrated in 57 of 65 (88%) of tissue sections classified as atherosclerotic and in 5 of 11 (45%) sections classified as minimally atherosclerotic. TNF was absent in 6 sections classified as normal. TNF positivity was found not only in the cytoplasm of macrophages, but also in the cytoplasm and attached to the cell membrane of smooth muscle cells and endothelial cells of the human atheroma. Because TNF is known to cause new vessel formation, hemorrhagic necrosis and increased thrombogenicity, it may play a role in the evolution of uncomplicated to complex atheroma.
Nonlinear dynamics is an exciting new way of looking at peculiarities that in the past have been ignored or explained away. We have attempted to give a general introduction to the basics of the mathematics, applications to cardiology, and a brief review of the new tools needed to use the concepts of nonlinear mathematics. The careful mathematical approach to problems in cardiac electrical dynamics and blood flow is opening a window on behaviors and mechanisms previously inaccessible.
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Insulin-like growth factor I (IGF-I) is a widely distributed mitogen that mediates the growth-promoting effects of platelet-derived growth factor in mesenchymal cells. We show that rat aortic IGF-I messenger RNA (mRNA) is induced 24 hours after deendothelialization, at a time when smooth muscle cell proliferation within the intima is still not apparent. After 7 days, IGF-I mRNA induction peaks at about ninefold control levels and then falls to about threefold 14 days after denudation when smooth muscle cell proliferation is at its peak. We also show that, of the 5' untranslated IGF-I mRNA transcripts, only the class C transcript is expressed and regulated in aortic tissue. In contrast, treatment of rats with supraphysiological doses of growth hormone, the major endocrine regulator of IGF-I gene expression, elicited only twofold induction of aortic IGF-I mRNA. Our findings suggest that IGF-I may be an important autocrine or paracrine regulator of smooth muscle cell proliferation and that it may be significant in determining the cellular response to arterial wall injury.
We used immunohistochemistry to detect tumor necrosis factor (TNF) and in situ hybridization to detect TNF messenger RNA (mRNA) in the intimal mesenchymal-appearing cells and in the medial smooth muscle cells of human atherosclerotic arteries. Medial smooth muscle cells showed localization of immunoreactive TNF on the cell surface and did not express TNF mRNA. Conversely, in intimal mesenchymal-appearing cells, TNF was localized in the cytoplasm and TNF mRNA was expressed by in situ hybridization. Thus 89% of intimal cells were immunohistochemically positive for TNF, 96% of them were positive by in situ hybridization, and 76% were positive for the smooth muscle cell marker, HHF35. Our results suggest that intimal mesenchymal-appearing cells are mostly, but not exclusively, derived from smooth muscle cells. These cells express TNF, whereas the medial smooth muscle cells in the atherosclerotic human arteries do not. The expression of TNF by these mesenchymal-appearing cells may have implications regarding the evolution of the atherosclerotic plaque.
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Because the extent of myocardial bulging after acute coronary occlusion is primarily dependent on wall tension, this study examined whether the decrease in systolic bulging with postextrasystolic potentiation was due to contractile reserve or to changes in loading conditions. Seven dogs were atrially paced at 100 beats/min after the sinus node was crushed and atrial extrasystoles were generated. The left ventricular minor axis diameter and segment lengths in the ischemic and nonischemic zones were measured with sonomicrometers. Wall tension was estimated using Laplace's law, and regional tension-length loops were determined. By 5 min after the left anterior descending coronary artery was occluded, there was regional bulging. Postextrasystolic potentiation diminished the extent of bulging by increasing both isovolumic and ejection percent systolic shortening (isovolumic -9.1 +/- 2.0% to -5.9 +/- 1.7%, p less than 0.008; ejection 2.2 +/- 0.7% to 4.3 +/- 2.0%, p less than 0.008). The tension-length loops after coronary occlusion showed an exponential upstroke and almost superimposed downstroke consistent with passive movement. The loops were unchanged by postextrasystolic potentiation. Wall tension data showed that bulging was reduced because of a shift down the tension-length curve as end-systolic wall tension was reduced by augmented nonischemic contraction. Similar results were seen at 60 min of coronary occlusion. This study demonstrates that the decrease in bulging seen with postextrasystolic potentiation is due to changes in loading conditions and not to contractile reserve.
The postoperative courses of 176 patients who underwent coronary artery bypass surgery for significant left main coronary artery stenosis were analyzed to determine which preoperative clinical and angiographic factors correlated best with outcome. Clinical variables included age, sex, New York Heart Association (NYHA) anginal class, presence of unstable angina, and surgical class. The angiographic variables included percentage of left main stenosis, presence of right coronary artery stenosis, coronary dominance, number of vessels diseased, myocardial jeopardy score, and ejection fraction. The overall perioperative mortality rate was 9.1%. There was a significant increase in perioperative mortality among female patients (p less than 0.05) and patients undergoing emergency surgery (p less than 0.05). Patients with left main stenosis of 80% or more or with balanced or left dominant circulation showed trends toward increased perioperative mortality. Life-table analysis showed that emergency surgery and left main stenosis of 80% or more correlated with increased long-term mortality (p less than 0.05). No other variable tested showed a significant correlation with either perioperative or long-term mortality. A comparison of these results with studies performed in the 1970s shows that there has been considerable change in those factors which place a patient at increased risk for mortality during surgical treatment of left main coronary artery stenosis.
Regional function assessed by ventriculography may be influenced by the hemodynamic effects of rapidly injecting ionic contrast medium. The importance of this after acute coronary occlusion was examined in eight open-chest, anesthetized dogs. The left anterior descending artery was ligated while sonomicrometric segment lengths in the ischemic (IZ) and nonischemic zones (NZ) were measured. Sodium methylglucamine diatrizoate (Renografin-76, 1 ml/kg) was rapidly injected over 3 seconds. Fifteen minutes later, the left ventricular end-diastolic pressure (LVEDP) was rapidly increased to the level reached during injection. Injecting the contrast increased the LVEDP (7.3 +/- 2.5 to 20.1 +/- 2.9 mm Hg, p less than 0.0001) to the same extent as raising LVEDP (7.6 +/- 2.5 to 10.1 +/- 2.9 mm Hg, p less than 0.0001). Injecting the contrast medium increased IZ total percent systolic shortening (% delta L) (-3.90 +/- 4.43% to -2.68 +/- 4.77%, p less than 0.001) by decreasing isovolumic bulging (-6.68 +/- 4.09% to -5.49 +/- 3.33%, p less than 0.001) with little change in ejection % delta L. NZ total % delta L tended to increase (19.03 +/- 6.53% to 19.94 +/- 6.27%, p = 0.015) because of augmented ejection % delta L (13.12 +/- 2.51% to 13.71 +/- 3.10%, p = 0.017) by the Starling mechanism. Increasing the LVEDP had the same effect on IZ and NZ regional shortening as injecting contrast. Thus regional shortening after acute coronary occlusion is affected by the changes in loading conditions with ionic contrast ventriculography.(ABSTRACT TRUNCATED AT 250 WORDS)
It has been shown that collaterals can develop rapidly during acute coronary occlusion, either due to thrombosis or during angioplasty (PTCA). However, the fate of well-developed collaterals immediately after a successful PTCA is unknown. Accordingly, 15 patients with Rentrop class 2 or 3 collaterals as visualized angiographically were studied immediately after successful single-vessel PTCA. The left anterior descending artery contained the stenosis in nine patients and the right coronary contained the stenosis in six patients. There was total occlusion of six vessels and subtotal occlusions of nine vessels pre PTCA. Immediately after PTCA, flow through the collaterals to the stenosed artery could no longer be visualized angiographically in eight patients (group 1), but remained faintly visible in seven patients (group 2). There was no difference between these two groups with regard to pre PTCA transstenotic pressure gradient (46 +/- 12 vs 42 +/- 14 mm Hg), post PTCA pressure gradient (13 +/- 7 vs 11 +/- 10 mm Hg), or post PTCA percent luminal diameter narrowing (26 +/- 18% vs 24 +/- 13%). These findings suggest that despite similar hemodynamic and angiographic improvement, the resolution of collaterals immediately after PTCA is variable.
Previous studies have characterised the motion of the myocardium using a linear time varying elastance model, ie, they have sought to characterise the relationship between left ventricular volume and internal pressure as linear, but with time varying slopes over the cardiac cycle. However, the motion of myocardium during regional ischaemia has not been characterized by such models. Studies of totally ischaemic tissue and of myocardium in diastole have characterised the relationship between tension or stress and segment length as exponential. It is the purpose of this study to present a new model in which myocardial contraction is expressed as an exponential, but time varying elastic relationship. In this model tension, T, is related to segment length according to the formula T = e alpha(t)L + beta, where alpha(t) rises with systole and falls in diastole. This model was applied to the motion of hypokinetic segments noted in a series of conscious dogs studied for other purposes. Hypokinetic segments display early systolic bulging, decreased systolic shortening, and early diastolic recoil. These particular types of segment motion are naturally predicted by this model. Furthermore, the motion of myocardial segments as they become increasingly ischaemic may be predicted, including a gradual shift to the right and narrowing of the tension-length loop. alpha was noted to be independent of loading change, and thus may be viewed as an index of contractility. This model thus predicts the pattern of motion of hypokinetic segments and provides new insight into myocardial contractility.
The hypothesis that there is a lateral border zone with function intermediate to adjacent ischaemic and non-ischaemic tissue was tested in 10 open chest anaesthetised dogs. Four pairs of segment length crystals were placed in parallel so as to span the ischaemic and non-ischaemic zones. Graded occlusion was produced with a screw clamp applied to a carotid to left anterior descending artery cannulation system. Contractile reserve was assessed using postextrasystolic potentiation. A balloon perfusion labelling system was used to label negatively the potentially ischaemic zone and quantify the admixture of ischaemic and non-ischaemic tissue in the lateral border zone, defined by the fraction of normal zone tissue. When the 40 crystal pairs from the 10 dogs were grouped according to fraction of normal zone tissue (FNZT), 13 were in the central ischaemic zone (FNZT less than 0.1), seven were in the border ischaemic zone (FNZT 0.1-0.5), five were in the border non-ischaemic zone (FNZT 0.5-1.0), and 15 were in the non-ischaemic zone (FNZT 1.0). When the lateral border zone is predominantly non-ischaemic tissue, the tissue behaves as though it is non-ischaemic. Segmental shortening before and after postextrasystolic potentiation in the border non-ischaemic zone and non-ischaemic zone did not change with ischaemia. When tissue in the lateral border zone is predominantly ischaemic, it behaves as though it is ischaemic. Segmental shortening decreased in parallel with progressive ischaemia in the border ischaemic zone and ischaemic zone. At total occlusion, segmental shortening in the border ischaemic zone was -2.3(5.9%) and in the ischaemic zone -3.5(3.6)% (NS).(ABSTRACT TRUNCATED AT 250 WORDS)
We studied how left ventricular loading conditions and the size of the ischemic zone affect regional segmental shortening (% delta L) in ischemic (IZ) and remote nonischemic zones (NZ) after acute coronary occlusion. Distal and proximal portions of the left anterior descending artery (group I, 10 dogs) or the left circumflex artery (group II, 10 dogs) were occluded in two stages. Segment length sonomicrometers were placed in the distal and proximal IZ and in the distal and proximal NZ. % delta L was divided into isovolumic and ejection phases. Left ventricular end-diastolic pressure (LVEDP) was decreased 3 +/- 1 mmHg by blood withdrawal and then increased 6 +/- 2 mmHg by blood transfusion before and after distal and proximal coronary occlusions. LVEDP was brought back to its initial value before distal and proximal coronary occlusions. Regional blood flow and total blood flow deficit were measured with microspheres. Similar results were obtained in group I and II experiments. After coronary occlusion, the IZ showed systolic bulging occurring primarily in isovolumic systole. In the NZ, total and isovolumic % delta L increased from control, whereas ejection % delta L did not change. As LVEDP was raised, IZ isovolumic bulging decreased and ejection % delta L was unchanged, whereas NZ isovolumic % delta L decreased and ejection % delta L increased. Thus IZ bulging and NZ isovolumic % delta L changed in opposite directions when load was varied. The larger IZ after proximal coronary occlusion tended to increase the amount of NZ isovolumic % delta L. In conclusion, at low LVEDP NZ augmentation is predominantly caused by an increase in isovolumic % delta L, whereas if LVEDP is increased it is because of an increase in ejection % delta L. In addition, in open-chest animals augmented contraction in the NZ may be related to the size of the IZ.
It has been previously shown that after acute coronary occlusion, the extent of systolic bulging is dependent on preload and the function of the remote nonischemic myocardium is influenced by the motion of the ischemic myocardium as well as by the loading conditions. To examine the isolated effects of changing afterload on the movement of acutely ischemic and nonischemic myocardium, seven open-chest, anesthetized dogs were paced from the left atrium at a rate of 100 beats/min after crushing of the sinus node. The pulmonary artery was perfused artificially and the left ventricular end-diastolic pressure (LVEDP) was carefully controlled with a right heart bypass system. Twenty minutes after occlusion of the left anterior descending artery, the peak left ventricular pressure (LVP) was adjusted to three levels (70, 90, and 110 mm Hg) by blood withdrawal or aortic constriction, while the LVEDP was kept constant (8.3 +/- 2.3 mm Hg). Segment length in the ischemic (IZ) and nonischemic zones (NZ) were measured with sonomicrometers and total, isovolumetric, and ejection systolic shortening (% delta L) were calculated. Changes in left ventricular minor-axis diameter were measured with diameter crystals. Increasing the peak LVP increased the LVP both at aortic valve opening and closing. To keep the LVEDP constant as peak LVP was increased, the cardiac output had to be decreased (p less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Determination of absolute lumen diameters has been shown to be useful in predicting the functional importance of a coronary stenosis. In this study, both single-plane and orthogonal biplane digital subtraction angiograms were obtained in human cadaver coronary arteries. A single absolute diameter was calculated at the site of greatest narrowing in 20 segments by two automated computerized algorithms. Minimum and maximum diameters at the site of the stenosis were measured from pathologic sections prepared after pressure fixation. Method 1, which determines the edges by means of the first derivative of the videodensity curve, derived absolute diameters that fell between the pathologic minimum and maximum in 10 of 20 segments. Method 2, which determines the edges by an average of the first and second derivatives of the videodensity change, derived absolute diameters that fell between the pathologic minimum and maximum diameters in 15 of 20 segments. Method 1 correlated well with the maximum pathologic diameter (r = .76) and less well with the minrmum pathologic diameter (r = .67). Method 2 correlated very well with the maximum pathologic diameter (r = .79) and also correlated well with the minimum pathologic diameter (r = .74). As would be expected, the computerized algorithms tended to overestimate the minimum pathologic diameter and to underestimate the maximum pathologic diameter. In six segments, two orthogonal views were analyzed; no further accuracy was discernible over single-plane determinations. Thus quantitative coronary angiography by digital subtraction angiography is sufficiently accurate to be of use in the measurement of the severity of a coronary stenosis.
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