The spiral orientation of left ventricular (LV) fibers suggests that twisting about the ventricular long axis of the apex with respect to the base, i.e., torsional deformation, may be characteristic of LV contraction. To demonstrate this twisting motion, 10 orthotopic human cardiac allograft recipients were studied with biplane cineradiography of tantalum helices implanted within the LV midwall at 12 specific sites. Counterclockwise twisting about the LV long axis (as reviewed from apex to base) accompanied ventricular ejection in all patients. Torsional deformation angles, measured relative to a reference minor axis at the base, were substantially smaller in the anteroapical wall, as compared with counterparts in the apical third of the inferior and lateral walls (anterior = 13.3 +/- 6.0 degrees, inferior = 18.7 +/- 6.3 degrees, and lateral = 23.4 +/- 10.7 degrees). Torsional angles at the midventricular level were roughly half as much and exhibited similar regional variabilities (anterior = 7.6 +/- 3.3 degrees, inferior = 9.0 +/- 3.3 degrees, lateral = 10.7 +/- 5.2 degrees, and septal = 8.8 +/- 3.8 degrees). Comparison of control beats and the initial beat after abrupt cessation of rapid atrial pacing (126 +/- 10 beats/min) with return to the control heart rate (96 +/- 9 beats/min) permitted the mild positive inotropic effect of tachycardia to be assessed at similar levels of ventricular load. Torsional deformation of the anteroapical and inferoapical sites increased significantly (p less than 0.05) over control values to 15.6 +/- 7.5 degrees and 21.2 +/- 5.5 degrees, respectively. In contrast, torsional deformation of the lateral wall was essentially unchanged. These data provide direct evidence for torsional deformation of the left ventricle in humans, demonstrate that torsion of the LV chamber is nonuniform, and suggest a dependence of LV torsion upon contractile strength that is attenuated in the lateral wall.
The present study was designed to investigate the anisotropy of systolic chord shortening in the lateral, inferior, septal, and anterior regions of the human left ventricle. At the time of surgery, 12 miniature radiopaque markers were implanted into the left ventricular midwall of the donor heart in 15 cardiac transplant recipients. Postoperative biplane cineradiograms were computer-analyzed to yield the three-dimensional coordinates of these markers at 16.7-msec intervals. In each of the four left ventricular regions, chords were constructed from a central marker to outlying markers, and the percent systolic shortening of each chord was calculated. In each region, chord angles were measured with respect to the circumferential direction (positive angles counterclockwise) and each chord was assigned to one of four angular groups: I. oblique, -45 +/- 22.5 degrees or 135 +/- 22.5 degrees; II. circumferential, 0 +/- 22.5 degrees or 180 +/- 22.5 degrees; III. oblique, 45 +/- 22.5 degrees or -135 +/- 22.5 degrees; or IV. longitudinal, 90 +/- 22.5 degrees. In the lateral, inferior, and septal regions, respectively, systolic shortening (mean +/- SD%) was significantly greater in Group I chords (19 +/- 5%, 17 +/- 5%, and 15 +/- 4%) than those in Group II (15 +/- 5%, 12 +/- 4%, and 11 +/- 4%), Group III (12 +/- 4%, 12 +/- 5%, and 11 +/- 4%), or Group IV (13 +/- 5%, 13 +/- 6%, and 12 +/- 5%). The anterior region was unique in exhibiting equal shortening in both Group I and Group II chords (16 +/- 5%), although the shortening of these chords was significantly greater than that of Group III and Group IV (12 +/- 5%) in this region. A cylindrical mathematical model was developed to relate longitudinal, circumferential, and oblique systolic shortening to torsional deformation about the long axis of the left ventricle. Torsional deformations measured in these 15 hearts were of sufficient magnitude and correct sense to agree with model predictions. These data suggest that torsional deformations of the left ventricle are of fundamental importance in linking the one-dimensional contraction of the helically wound myocytes to the three-dimensional anisotropic systolic shortening encountered in the transplanted human heart.
Traditional left ventricular (LV) function curves are frequently depressed in patients with acute lung injury. Similar findings in pentobarbital sodium-anesthetized dogs with oleic acid lung injury (OALI) have been observed. To test the hypothesis that acute OALI produces a significant injury to the heart, the LV mechanics of pentobarbital-anesthetized dogs with (n = 6) and without (n = 6) OALI were evaluated. End-systolic force-length and force-velocity relations determined echocardiographically during afterload manipulation with sodium nitroprusside demonstrated a marked deterioration in LV shortening characteristics over 90 min in both groups of pentobarbital-anesthetized dogs. In contrast, LV mechanics studied using the same protocol in fentanyl-anesthetized dogs were unchanged in both the injured (n = 6) and noninjured (n = 6) lung groups. Comparisons with data acquired over a wide range of LV afterload from six conscious, instrumented dogs showed that LV contractile state was normal to slightly increased with fentanyl and markedly depressed with pentobarbital. Diastolic properties, as assessed by end-diastolic pressure-dimension relations, were essentially unchanged in all anesthetized animals. We conclude that OALI has no effect on LV systolic or diastolic mechanics; the LV dysfunction attributed to OALI in previous studies is due to an acute, severe cardiomyopathy induced by pentobarbital; and unlike pentobarbital, anesthesia with fentanyl has no discernible time-dependent effect on LV mechanics. These findings have important implications for future studies of canine cardiovascular physiology employing anesthetized animal preparations.
Alterations in loading conditions and muscle length influence the electrophysiology of ventricular myocardium and may play a role in arrhythmogenesis in globally dilated or dyskinetic ventricles. To test the hypothesis that stretch can initiate arrhythmias in normal myocardium, the response to graded mechanical stretch was studied in seven isolated blood-perfused canine ventricles. After eight conditioning contractions produced by His bundle pacing (2 Hz), global stretch of the ventricle was produced by a servocontrolled pump that abruptly increased ventricular volume by a precise amount (delta V) during early diastole and then returned ventricular volume to the initial holding volume (Vi). Ventricular premature contractions were readily produced; ventricular couplets and short runs of ventricular tachycardia were occasionally elicited. The probability of a stretch-induced arrhythmia was determined from multiple alternating sequences in which a stretch of known amplitude (delta V) or no stretch was delivered. As delta V was increased, the probability of a stretch-induced arrhythmia was low initially, increased sharply after a threshold was exceeded, and approaching 100% with physiological volumes. With Vi set to a standard value of 20 ml, corresponding to end-diastolic pressure of 5.3 +/- 5.2 mm Hg (mean +/- SD), the delta V resulting in a 50% chance of a stretch-induced arrhythmia (delta V50) was 15.0 +/- 1.6 ml. A decline in delta V50 was consistently observed when Vi was increased. While delta V50 values were remarkably similar (10.7% coefficient of variation), the pressure at the time the ventricular premature depolarization was triggered was highly variable for different ventricles; this finding suggests that myocardial strain is more important than absolute level of wall stress in the initiation of these arrhythmias. These results demonstrate that myocardial stretch predictably initiates arrhythmias and that the susceptibility to stretch-induced arrhythmias is enhanced by ventricular dilatation. Thus, ventricular ectopy in patients with regionally or globally dilated hearts may arise, in part, by a mechanism of myocardial stretch.
BACKGROUND Left ventricular (LV) twist, the longitudinal gradient of circumferential rotation about the LV long axis, may play an important role in the storage of potential energy at end systole and its subsequent release as elastic recoil during early diastole; however, the effects of load and inotropic state on LV systolic twist and diastolic untwist in human subjects have not previously been characterized. METHODS AND RESULTS Six cardiac transplant recipients with 12 implanted radiopaque midwall LV myocardial markers were studied 1 year after transplantation. Biplane cinefluoroscopic marker images and LV pressure were recorded during control conditions and after afterload augmentation (methoxamine, 5 to 10 micrograms.kg-1 x min-1), inotropic stimulation (dobutamine, 5 micrograms.kg-1 x min-1), and preload augmentation (volume loading with normal saline). Systolic twist dynamics were assessed by maximum twist (Tmax[rad/cm]), peak negative twist rate (-dT/dtmin[rad.cm-1 x s-1]), and the slope of the twist normalized-ejection fraction relation (T-nEFR, Msys[rad/cm]) during systole. Diastolic untwist was assessed by the peak positive untwist rate (+dT/dtmax [rad.cm-1 x s-1]) and the slopes (rad/cm) of the T-nEFR during early diastole (Mear-dia) and mid diastole (Mmid-dia). Compared with control values, LV pressure and volume loading had no significant effect on Tmax, -dT/dtmin, or Msys; however, inotropic stimulation significantly increased all parameters describing systolic twist (Tmax: -0.10 +/- 0.03 versus -0.06 +/- 0.02 rad/cm, P < .001; -dT/dtmin: -0.72 +/- 0.19 versus -0.44 +/- 0.22 rad.cm-1 x s-1, P < .001; Msys: -0.10 +/- 0.03 versus -0.06 +/- 0.01 rad/cm, P < .001). Pressure loading had no effect on early diastolic untwisting; however, dobutamine significantly increased M(ear)-dia (-0.24 +/- 0.06 versus -0.13 +/- 0.04 rad/cm, P < .0001) and +dT/dtmax (0.78 +/- 0.24 versus 0.45 +/- 0.16 rad.cm-1 x s-1, P < .001). Conversely, volume loading significantly decreased M(ear)-dia (-0.08 +/- 0.04 versus -0.13 +/- 0.04 rad/cm, P < .05). M(ear)-dia correlated directly with LV contractile state (as assessed as maximum dP/dt, r = .60, P < .0001) and inversely with end-systolic volume (r = -.87, P < .0001) but was unrelated to stroke volume (r = .08, P = .30) or LV afterload (estimated as effective arterial elastance, r = .08, P = .29). Mmid-dia did not change during any intervention. CONCLUSIONS In conscious human transplant patients, (1) pressure and volume loading do not affect systolic LV twist; (2) dobutamine augments systolic twist and early diastolic untwisting, suggesting more end-systolic potential energy storage and early diastolic elastic recoil with enhanced inotropic state; (3) volume loading decreases early diastolic untwisting, possibly reflecting diminished recoil forces after preload augmentation associated with larger end-systolic volumes (ESV); and (4) M(ear)-dia correlates strongly with ESV (in an inverse fashion), and less strongly, but directly, with LV dP/dtmax.
Ventricular arrhythmias can be initiated by a mechanism of transient diastolic dilation. To test the hypothesis that Ca2+ release from sarcoplasmic reticulum (SR) is important in initiation of such stretch-induced arrhythmias (SIAs), we studied effects of ryanodine in an isolated canine heart model. Arrhythmias were induced by a computerized ventricular volume servo-pump system that transiently increased left ventricular volume by precise amounts (delta V) during diastole. The probability of eliciting an SIA (PSIA) was compared at the minimum delta V that resulted in PSIA of >5 or = 90% under baseline conditions. Block of SR Ca2+ release with 10(-5) M ryanodine in 11 ventricles produced mild inhibition of SIAs, reducing PSIA by 19.4% (P = 0.039). Because ryanodine produces leakage of SR Ca2+ at low concentration and block of SR Ca2+ release at high concentration, ryanodine concentration was varied from 10(-9) to 10(-5) M in six ventricles. Ryanodine had minimal effect on PSIA over this concentration range. In six ventricles with elevated intracellular Ca2+ produced by pretreatment with 0.1-0.3 microM strophanthidin, 10(-5) M ryanodine did not significantly reduce PSIA. Probability of inducing ventricular pairs or nonsustained ventricular tachycardia was greater in strophanthidin-treated ventricles than in controls, but induction of these repetitive ventricular beats in the strophanthidin group was virtually abolished by addition of 10(-5) M ryanodine.(ABSTRACT TRUNCATED AT 250 WORDS)
Recently several studies have shown that during incremental exercise in which velocity is increased, the anaerobic threshold (AT) corresponds significantly with a deflection in heart rate (HR). These studies involved well-trained athletes, most of whom participated in lower extremity activities. The purpose of this study was to determine whether AT could be determined in a similar manner in untrained individuals performing arm exercise. Ten healthy untrained males ages 20 to 27 cranked a modified cycle ergometer until exhaustion using two different arm tests. In a “velocity” test, exercise intensity was increased 6.94 watts every 30 seconds by incrementing velocity 2 km·hr−1 while maintaining a constant braking force of 1.5 kg. Exercise intensity was incremented by 6.25 watts in a “resistance” test by increasing the braking force 0.12 kg every 30 seconds while maintaining velocity at 18 km·hr−1. At the end of each 30-second period of each test, HR and expiratory gases were measured. Computer analysis of the HR response indicated that HR remained linear in all subjects throughout the range of exercise in both tests. Computer analysis of the VE response with each test revealed a significant deflection in VE that occurred between an average of 62 and 66 percent of peak O2, for the “velocity” and “resistance” tests respectively. Because there was no statistically significant breakpoint in HR throughout the range of exercise with either test, HR as a single measurement should not be used as a reliable predictor of AT in individuals performing arm exercise.
