IntroductionCardiac adaptation to hemodynamic stress involves both quantitative (hypertrophy) and qualitative (pattern of gene expression) changes. Our previous studies have shown that advancing age in the rat is associated with diminished capacity to develop left ventricular hypertrophy in response to either ascending aortic constriction (AoC). In this study, we examined whether the expression of protooncogenes and contractile protein genes in response to AoC differs between adult (9-mo-old) and old (18-mo-old) rats. RNA was isolated from the left ventricles of AoC animals of both age groups subjected to a similar hemodynamic stress. Immediately after AoC, the levels of the ventricular expression ofc-fos and c-jun protooncogenes were markedly lower in the old rats than in the adult animals. 5 d after the operation, the ratio of,-to a-myosin heavy chain mRNAs increased significantly after AoC in both age groups. In contrast, AoC was associated with a marked reduction in the levels of mRNAs encoding sarcoplasmic reticulum Ca2"-ATPase (by 69%) and cardiac calsequestrin (by 49%) in the old rats but not in the adults. The mRNAs encoding atrial natriuretic factor and skeletal a-actin increased in response to AoC only in the adult rats. There were no significant differences in expression of the cardiac a-actin mRNA among the experimental groups. These data suggest that (a) the expression of protooncogenes in response to acute pressure overload is significantly reduced in the aged rats and (b) the pattern of expression of the contractile protein gene in response to AoC in the old rats differs qualitatively as well as quantitatively from that in younger animals. These age-related differences may play a role in the higher frequency of heart failure in the aged during hemodynamic stress. (J. Clin. Invest. 1992. 89:939-946.) Key words: actin . myosin heavy chain * calsequestrin * Ca2+-ATPase -atrial natriuretic factor

Chronic hypoxia increased myocardial tolerance to ischaemia, and acute ischaemic preconditioning increased the tolerance further. Thus chronic hypoxia and acute ischaemic preconditioning independently activate protective mechanisms against ischaemia; the mechanisms may differ between the two types of insult.

To test the hypothesis that the capacity to develop left ventricular (LV) hypertrophy might diminish with advancing age, we examined the hypertrophic response to ascending aortic constriction in 3 groups of adult Fischer 344 rats (9 months, 18 months, and 22 months of age). Aortic constriction was created so that aortic cross-sectional areas would be the same for the 3 groups of rats. Four weeks after imposition of aortic constriction, there was no significant difference in peak LV pressure, peak-to-peak and mean systolic pressure gradients between left ventricle and aorta, cardiac output, LV minute work, or cross-sectional area of the aortic constrictions in the 3 groups. In 9-month-old aortic-constricted rats, LV dry wt (LVDW)/body wt, LVDW/tibial length, and myocyte width increased by 23% (p less than 0.01), 14% (p less than 0.01), and 27% (p less than 0.01), respectively, compared with sham-operated rats. In contrast, in 18-month-old and 22-month-old aortic-constricted rats, LVDW/body wt and LVDW/tibial length were unchanged compared with sham-operated controls, and increases in myocyte width were only modest 4 weeks following constriction. RNA concentration in the myocardium 5 days after constriction increased by 21% (p less than 0.001) in 9-month-old rats but showed no significant rise in 18-month-old rats. These results suggest that advancing age is associated with a diminished capacity to develop myocardial hypertrophy in response to acute pressure overload and that a reduced ability to synthesize protein may be one of the major contributing factors to a diminished capacity for hypertrophy in advanced age.

The transradial approach for catheterization is becoming increasingly more popular. At present, the choice of the right or left radial artery depends on the operator's preference. We examined how the laterality influenced the effectiveness of the approach. Employing Judkins-type catheters, we performed coronary angiography in 232 patients with the left approach and in 205 patients with the right approach. Although access time did not differ between the two groups of patients, the duration of catheter manipulation was shorter in the left- than in the right-approach group (11.7 +/- 5.9 vs. 9.8 +/- 4.4 min; P < 0.001). Because of the shorter duration of catheter manipulation, the total procedural duration was shorter in the left-approach group (13.7 +/- 6.4 vs. 11.4 +/- 4.8 min; P < 0.001). The fluoroscopy time was shorter in the left- than in the right-approach group (3.7 +/- 2.5 vs. 5.0 +/- 3.3 min; P < 0.001). The amount of contrast material did not differ between the groups (79 +/- 27 vs. 83 +/- 25 ml). The rate of guidewire usage to engage the coronary ostium was higher in the right- than in the left-approach group because of the severe tortuosity of the right subclavian artery (20/205 vs. 0/232; P < 0.001). Thus, for operators with significant experience, the left radial approach may provide increased procedural efficacy for coronary angiography compared to the right radial approach.

To test the hypothesis that the capacity for left ventricular (LV) adaptation to volume overload might diminish with age, we examined the hemodynamics and degree of myocardial hypertrophy in response to aortic insufficiency in young adult (9 mo) and old (18 or 22 mo) Fischer rats. Before, immediately after, and at 2 and 4 wk after creating aortic insufficiency, LV and aortic pressures were measured using a catheterization technique. 4 wk after surgery, we measured aortic flow, and estimated the LV passive pressure-volume relationship and the degree of LV hypertrophy after killing. Immediately after the surgical creation of aortic insufficiency, both young and old rats showed similar elevation of LV end-diastolic pressure (from 4.8±0.6 to 12.0±1.5 mmHg in the young rats, P < 0.01; from 4.9±0.4 to 11.0±0.7 mmHg in the old rats, P < 0.01). In the young rats LV, end-diastolic pressure decreased to 8.0±1.0 and to 8.5±0.9 mmHg at 2 and 4 wk (P < 0.05). In contrast, LV end-diastolic pressure at 2 (16.9±3.1 mmHg) and 4 wk (16.1±2.7 mmHg) in the old rats was even higher, compared with the values measured immediately after aortic insufficiency. At 4 wk, LV end-diastolic meridional wall stress (calculated from the in vivo LV end-diastolic pressure, and the pressure-volume relationship and muscle mass obtained after killing) was higher in the old rats than in the young rats. In the young rats, the diastolic pressure-volume relationship at 4 wk shifted to the right (P < 0.01), and LV dry weight, LV dry weight/tibial length, and protein content of the LV myocardium increased by 26% (P < 0.01), 24% (P < 0.01), and 33% (P < 0.01), respectively. However, old rats with aortic insufficiency did not show a significant change in the pressure-volume relationship, dry weight, or protein content at 4 wk. These results suggest that advanced age diminishes the capacity for LV hypertrophy in response to a volume overload, and this reduced LV hypertrophic response in the old rats resulted in persistent elevation of LV end-diastolic pressure and wall stress.

The radial artery approach is becoming more popular for diagnostic cardiac catheterization and interventional procedures because of its lower incidence of access site complications and decreased patient discomfort after the procedure. However, Allen's test reveals inadequate blood supply through the ulnar artery to the hand, and therefore the approach does not seem to be suitable in 10%-30% of patients. Here we demonstrated a new percutaneous ulnar artery approach for coronary angiography in nine patients. We succeeded in obtaining an entry site into the left ulnar artery in seven patients. The average time for cannulation and that for catheterization procedure were comparable with those of the radial approach previously reported from other laboratories. Complications such as bleeding, loss of an ulnar pulse, ulnar nerve injury, and the formation of an aneurysm or fistula were not observed in any patient. The ulnar approach may be another technique that decreases patient discomfort and risk, while preserving the radial artery as a potential coronary bypass graft for surgical myocardial revascularization. Cathet Cardiovasc Intervent 2001;53:410-414.

By using excised postmortem hearts obtained from 15 mongrel dogs with the pericardium intact, we investigated mechanical interactions between the four heart chambers from the standpoint of ventricular pressure-volume relationships. The interactions investigated were those between (1) the atrium and the ventricle, (2) the right ventricle and left ventricles, (3) the atrium and one ventricle vs. the other ventricle, and finally (4) the left and right atrium and the right ventricle vs. the left ventricle. For these purposes, we inserted compliant balloons into the four heart chambers without injuring the pericardium, i.e., we incised the base of the atria which was not covered with the pericardium. We obtained the right and/or left ventricular pressure-volume relationships under a constant pressure in three other heart chambers by changing the height of the reservoir connected to each balloon. As a result, both ventricular pressure-volume relationships were hardly affected by an increase in the atrial pressure ranging from 5 to 30 cm H2O with the pericardium removed, although the ventricle became less compliant due to an increase of the same magnitude of the opposite ventricular pressure. On the other hand, the effect of an increase in atrial pressure was distinct with the pericardium intact. Also, all mechanical interactions were enhanced dramatically with the intact pericardium. Thus, the pericardium plays an important role in these mechanical interactions, especially when the filling pressures of all heart chambers increase simultaneously. Clinically, these findings may be important to understanding ventricular functions as related to various heart disease-especially acute heart failure.

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