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We investigated the relationship between regional myocardial blood flow (MBF) and segmental shortening in 17 open-chest dogs. The left anterior descending coronary artery was cannulated and perfused from the left carotid while measuring perfusion pressure. Graded occlusion was produced by a screw clamp. Extent of occlusion was monitored by perfusion pressure. Percent systolic shortening (% delta L) was measured using ultrasonic crystals implanted in normal and ischemic endocardium and ischemic epicardium. MBF was measured in ischemic and normal endocardium and epicardium with tracer microspheres. Dogs underwent 1 to 4 grades of coronary stenosis. Myocardial blood flow both to endocardium and epicardium was found to be linearly related to diastolic perfusion pressure below 50 mmHg (r = 0.803 and 0.748, respectively). Normalized % delta L (N% delta L) was best related to fraction normal zone MBF in the endocardium by the sigmoidal equation, N% delta L = e9.01 MBF-4.03/1 + e9.01 MBF-4.03. % delta L was only weakly related to myocardial blood flow in the epicardium (r = 0.584), and, in four dogs, % delta L was zero in the epicardium despite normal regional blood flow. However, % delta L in the epicardium was linearly related to % delta L in the endocardium (r = 0.78). Thus, endocardial wall motion is related to MBF by a sigmoidal relationship while epicardial wall motion is tethered to endocardial wall motion.

To determine the mechanical factors affecting regional segmental motion after acute coronary occlusion, we studied seven conscious dogs, instrumented with sonomicrometers. Loading conditions were changed by the withdrawal of 500 ml of blood and the transfusion of 800 ml of blood. To express segmental motion, percent systolic shortening, percent systolic elongation, and early diastolic shortening were calculated. Blood withdrawal decreased left ventricular preload, increased percent systolic elongation (from 6.9 +/- 3.1% to 9.9 +/- 3.5%) and early diastolic shortening (12.9 +/- 5.3% to 16.6 +/- 5.3%), and decreased percent systolic shortening. Blood transfusion increased left ventricular preload, decreased percent systolic elongation (to 5.2 +/- 1.8%) and early diastolic shortening (8.8 +/- 2.9%), and increased percent systolic shortening. Manipulation of loading did not change regional myocardial blood flow. In acutely ischemic myocardium, the tension-length loop showed an exponential upstroke during isovolumic systole and a nearly superimposed exponential downstroke during the isovolumic relaxation phase after systole, compatible with essentially passive movement as seen with an elastic material. The changes in loading conditions affected the tension-length curve to a very minor extent. The uniformity of the curve and its exponential shape explain the load-dependency of systolic bulging and segmental motion. It is concluded that systolic bulging depends on the change in the preload tension due to the compliant portion of tension-length curve, and that shortening of ischemic myocardium during the isovolumic relaxation phase is a completely passive phenomenon.

The calcium flux inhibitors nifedipine and verapamil have recently been used in the setting of both classical Heberden's and variant angina. It has also been suggested that these agents may preserve function and viability of threatened myocardium. The effects of these agents on the relationship between myocardial blood flow and contraction in the setting of partial coronary occlusion is unknown. Thus 39 open-chest dogs underwent partial coronary occlusion to diastolic perfusion pressures of 25 or 40 mm Hg. The dogs then received intracoronary infusions of 10 micrograms nifedipine or 100 micrograms verapamil. Myocardial blood flow was measured with tracer microspheres and myocardial shortening was assessed with ultrasonic crystals. At 25 mm Hg nifedipine improved myocardial shortening while blood flow did not change. In contrast, verapamil caused shortening to be abolished but also did not change blood flow. At 40 mm Hg nifedipine, while not affecting shortening, caused a "redistribution" of blood flow from endocardium to epicardium; in contrast, verapamil again caused shortening to be abolished, but only increased epicardial blood flow leaving endocardial flow intact. Thus verapamil and nifedipine have differing effects. Nifedipine is a potent vasodilator at doses having no negative inotropic effects. In addition, nifedipine can cause a transmural "redistribution" of blood flow from endocardium to epicardium. In contrast, verapamil is also a potent vasodilator, but has profound negative inotropic effects.

The effects of intracoronary nitroglycerin were determined in 21 open-chest dogs. Six dogs with severe stenosis (25 mm Hg diastolic perfusion pressure) and nine dogs with moderate stenosis (40 mm Hg) received a 12 micrograms bolus followed by 44 micrograms/min intracoronary nitroglycerin. In addition, six dogs with moderate stenosis (40 mm Hg) received 5 micrograms followed by 5 micrograms/min nitroglycerin. Myocardial blood flow was measured with radioactive microspheres and segment shortening with ultrasonic crystals. At 40 mm Hg, high-dose but not low-dose nitroglycerin raised epicardial blood flow, while at 25 mm Hg nitroglycerin had no effect. Subendocardial blood flow was not affected in any group. Partial occlusion resulted in a decrease in segment shortening in the 25 mm Hg group but not at 40 mm Hg. High-dose nitroglycerin had no effect on shortening at either level of occlusion. Thus, in the presence of coronary vascular reserve, high-dose nitroglycerin may overcome coronary autoregulation. A dose equivalent to one that simulates the amount of nitroglycerin delivered to the coronary circulation by a systemic infusion did not affect myocardial blood flow. In addition, even a large dose of nitroglycerin did not affect segment shortening.

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.

Nifedipine has been proposed as an agent to preserve viability and function of ischemic myocardium. We studied 23 open-chest dogs that underwent carotid-to-left anterior coronary artery perfusion with flow probe and perfusion pressure monitoring. Segment length was measured with ultrasonic crystals in the ischemic and nonischemic endocardium. Myocardial blood flow was measured with radioactive microspheres. Partial coronary occlusion was performed to 25 mm Hg diastolic perfusion pressure. Ten dogs received intracoronary nifedipine, 10 micrograms, and 13 dogs received i.v. nifedipine, 3 micrograms/kg/min. Nifedipine resulted in an increase in segmental shortening in both groups, but nonischemic zone shortening did not change in either group. Nifedipine did not affect myocardial blood flow in the ischemic zone, but increased flow in the nonischemic zone in the group that received i.v. nifedipine. Thus, nifedipine appears to have a direct beneficial effect on ischemic myocardium.

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 quantitative effects of graded ischemia on the phases of contraction in ischemic and nonischemic myocardium were studied in 10 open-chest dogs. During progressive coronary stenosis, an index of the overall severity of ischemia, total myocardial blood flow deficit (TMFD), was measured using microspheres. Segment shortening (% delta L) during the isovolumic and ejection phases of systole in the ischemic and nonischemic zones was obtained with ultrasonic crystals. In the ischemic zone, total systolic and ejection phase % delta L decreased progressively as stenosis increased; isovolumic phase % delta L showed segment elongation (bulging) during mild ischemia, which was unchanged as ischemia became severe. Total % delta L in the nonischemic zone increased progressively with increasing stenosis, reaching 132 +/- 20% of the control value when TMFD was 24.8 +/- 6.5% of total expected left ventricular (LV) myocardial blood flow. The increase in total % delta L was entirely attributable to increased ejection % delta L and correlated with indices of preload (multivariate r = 0.65) and afterload (multivariate r = 0.62). Multiple linear regression analysis revealed that augmented contraction in the nonischemic zone was best described (multivariate r = 0.94) by a combination of four hemodynamic variables estimating LV preload and afterload, which correlated in turn with the overall severity of ischemia. Thus systolic bulging in the ischemic zone is primarily an isovolumic phase phenomenon that develops initially with mild ischemia. Little additional change occurs in the isovolumic phase as ischemic severity increases, although further reductions in shortening occur in the ejection phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Both nifedipine and nitroglycerin are used to treat angina pectoris. The comparative effects of these agents on myocardial blood flow and contraction in the setting of flow-limiting coronary stenosis are poorly understood. Thus 24 open chest dogs underwent carotid to left anterior descending coronary arterial perfusion with coronary flow probe and perfusion pressure monitoring. Segment length was measured with ultrasonic crystals in the subendocardial ischemic and nonischemic zones. Myocardial blood flow was measured with radioactive microspheres. Partial coronary occlusion was performed to attain a diastolic perfusion pressure of 40 mm Hg. Twelve dogs received intravenous nifedipine, 3 micrograms/kg per min, and 12 received intravenous nitroglycerin to reduce aortic pressure by 20 mm Hg. Partial occlusion resulted in a slight but significant decrease in segment shortening in the ischemic zone. Neither nitroglycerin nor nifedipine affected shortening in the ischemic zone. After occlusion, blood flow decreased in the subendocardial ischemic zone but was unchanged in the subepicardium. Nifedipine increased subendocardial blood flow in the nonischemic zone and decreased it in the ischemic zone but caused no change in subepicardial flow in the ischemic zone. In contrast, nitroglycerin decreased subendocardial and subepicardial blood flow in both the ischemic and nonischemic zones. In the setting of coronary stenosis, different classes of vasodilators may have varying effects on myocardial blood flow, suggesting different sites and mechanisms of action. In addition, segment function may not always reflect changes in myocardial blood flow.

Several aspects of regional ischemic myocardial function determined by segment motion are discussed, based on our studies. Although global left ventricular function decreased progressively as the global severity of myocardial ischemia increased, there are several possible factors which may modify this relationship. As for the site of the ischemic area, occlusion of the left anterior descending artery resulted in a greater decrease in the left ventricular ejection fraction than occlusion of the left circumflex artery. Interaction between the ischemic myocardium and the non-ischemic myocardium may be a multifactorial phenomenon rather than simple tandem stretching. The segment length motion during acute ischemia appears to be complicated. The segment motion of the severe ischemic myocardium during systole and diastole was explained for the most part by a uniform tension-length curve which was independent of changes in the loading condition. This non-linear elastic property was fundamental to the production of segment motion asynchrony. The wall motion of the hypokinetic segment might be explained by a combination of the active change in myocardial stiffness and the non-linear elastic property of the myocardium.

The effect of graded coronary occlusion on myocardial shortening in different zones of the left ventricle is not clear. Therefore, in 15 dogs ultrasonic crystals were used to evaluate the effect of graded coronary occlusion on subendocardial and subepicardial contraction in both the left anterior descending coronary artery (LAD) and left circumflex coronary artery (Circ) distributions. Subepicardial shortening was evaluated along both the long and short axes. In the LAD zones, segment shortening decreased in parallel in the subendocardium and subepicardium. In the circumflex zone subendocardial and subepicardial long axis shortening fell off in parallel, while subepicardial short axis shortening fell off more rapidly. Thus there is a close relationship between endocardial and epicardial segment shortening following graded coronary occlusion. In the circumflex zone, however, fiber orientation may affect the measurement of segment motion.