Effects of CardioPhase
on Myocardial Damage
DU Xiao-yang, CardioPhase Research
Group, Xi’an Jiaotong University, Xi’an 710061,
China
Abstract: CardioPhase is a new traditional
Chinese compound possessing the ability to support cardiovascular
health. On the basis of previous long-term clinical results
the State Ministry of Health approved planned phase 2 clinical
trials of CardioPhase. Beginning in December 1992 we observed
the effects of CardioPhase on patients with myocardial damage
induced by various organic cardiopathy. We estimated the clinical
effects of CardioPhase and provided vital scientific evidence
for its wide clinical application.
Of the 304 patients completing
the Phase 2 CardioPhase trial, 100 demonstrated Effective
Improvement of symptoms, 189 showed Improvement
and 15 cases were Without Improvement. The total
effective rate regarding symptoms was 95.06%. As determined
by ECGs, Effective Improvement was found in 86 cases,
Improvement in 104 cases, and 114 cases were
Without Improvement, for a total effective rate of 62.50%.
Additionally, 100 patients receiving CardioPhase were compared
with 100 patients using propranolol as the positive contrast
drug. The CardioPhase group showed statistically significant
results over the propranolol group.
Experimental
Methods
General
Information
We observed a total of 404 patients (236 male, 171 female)
with myocardial damage induced by various organic cardiopathies.
Of these, 325 patients presented with arterial disorders,
including coronary artery disease (CAD), angina pectoris (AP)
and hypertensive heart disease. 79 cases showed damage to
heart tissue, including cardiomyopathy (CM) and myocarditis
(MC).
200 patients were selected
and randomly divided into two groups. 100 patients were treated
with CardioPhase (CardioPhase Group A) and 100 patients were
treated with propranolol (Propranolol Contrast Group). CardioPhase
was provided by Xi’an Medical University, and propranolol
(propranolol hydrochloride) was obtained from Shantou Chemical
Pharmacy Factory (Shantou, Guangdong, China, No. C6-063),
with lot number of 910627. The remaining 204 patients, comprising
64 outpatients and 140 hospitalized patients, were treated
with CardioPhase (CardioPhase Group B). As a group, the total
of 304 patients receiving CardioPhase are referred to as CardioPhase
Group C (All). Patient gender, age, course of disease and
site of treatment are presented in Tables 1 and 2.
Table 1.
Group |
Male |
Female |
Mean
Age
(in years) |
Mean
Course of Disease (in years) |
Propranolol Contrast Group |
62 |
38 |
55.71 |
4.47 |
| CardioPhase Group A
(n=100) |
55 |
45 |
55.47 |
4.06 |
CardioPhase Group B
(n=204) |
116 |
88 |
56.14 |
4.09 |
Table
1. Patient gender, age and course of illness. |
Table 2.
Group |
Outpatients |
Hospitalized
Patients |
Ratio
of Outpatients to Hospitalized Patients |
Propranolol Contrast Group |
0 |
100 |
100% |
| CardioPhase Group A |
0 |
100 |
100% |
CardioPhase Group B |
64 |
140 |
31.37% |
Table
2. Site of patient treatment. |
Subjects
Patients were admitted on the basis of Western medical diagnostic
criteria as outlined in “Ischaemic Heart Disease
Diagnosis and Naming Standards” (Circulation 59:606,
1979) developed by the International Standards Heart Institute
and WHO. Cardiopathies were diagnosed on the basis of presenting
with evidence of myocardial damage as measured by alterations
of electrocardiograms (ECG). Excluded from the study were
patients with symptoms of atrioventricular block and other
symptoms that could induce secondary S-T section or T wave
alterations.
Methods
Patients received either CardioPhase, three times daily, or
propranolol, three times daily. At the end of six weeks treatment
was halted and the results analyzed. Observation data included
blood pressure, heart rate, chest X-ray, ECG and liver and
kidney function tests. Blood samples were measured for plasma
lipid peroxide (LPO) concentrations and superoxide dismutase
(SOD) activity.
Results
The observed
therapeutic effects of CardioPhase were classified in one
of three categories:
Effective defined
as the disappearance of clinical symptoms, recovery of the
characteristics of ST-T segment and obvious improvement
of electrocardiogram (ECG), i.e. negative T waves converted
into positive T waves.
Improved
defined as clinical symptoms improving in one or more than
one class of symptoms. ECG scores were improved but not
reaching normal values, i.e. low S-T section elevated to
over 0.05 mV, or high S-T section lowered to 0.05~0.1 mV;
negative T waves were improved; clinical symptoms were improved
though ECG remained unchanged.
Ineffective defined
as clinical symptoms and ECG remaining unchanged.
The
Total Therapeutic Effect
The therapeutic effects of
three groups are presented in Table 3.
Table 3.
Therapeutic
Effect |
Propranolol
Contrast Group |
CardioPhase
Group A (100) |
CardioPhase
Group C (All) |
Effective |
27 |
33 |
86 |
| Improved |
55 |
59 |
203 |
No Effect |
19 |
8 |
15 |
| Total |
100 |
100 |
304 |
| Total Effective Rate |
81% |
92% |
95% |
Table
3. Therapeutic effects of each group. |
As shown in Table 3, the total
effective rate was 81% in the Propranolol Contrast Group,
92% in CardioPhase Group A, and 95% in CardioPhase Group C.
The therapeutic effects observed in the CardioPhase treated-groups
were significantly better than those in the propranolol contrast
group.
Therapeutic
Effect on ECG
Table 4 illustrates that the therapeutic effects
on myocardial damage, as measured by ECG, were similar among
the three groups.
Table 4.
Therapeutic
Effect |
Propranolol
Contrast Group |
CardioPhase
Group A (100) |
CardioPhase
Group C (All) |
Effective |
31 |
33 |
86 |
| Improved |
28 |
31 |
104 |
No Effect |
41 |
36 |
114 |
| Total |
100 |
100 |
304 |
| Total Effective Rate |
59% |
64% |
62.5% |
Table
4. ECG effects of each group. |
Effect
on Clinical Symptoms
Effects on clinical symptoms are displayed in Tables
5 and 6.
Table 5.
Therapeutic
Effect |
Propranolol
Contrast Group (n=100) |
| Angina |
Arrhythmia |
Breath
Holding |
Dizziness |
Shortness
of Breath |
Total |
| |
n=78 |
n=63 |
n=62 |
n=43 |
n=57 |
n=303 |
Effective |
61 |
54 |
46 |
30 |
41 |
232 |
| Improved |
11 |
5 |
10 |
6 |
8 |
40 |
No Effect |
6 |
4 |
6 |
7 |
8 |
31 |
| Total Effective Rate |
92.31% |
93.65% |
90.32% |
83.72% |
85.90% |
89.76% |
Therapeutic
Effect |
CardioPhase
Treated Group (n=100) |
| Angina |
Arrhythmia |
Breath
Holding |
Dizziness |
Shortness
of Breath |
Total |
| |
n=75 |
n=71 |
n=57 |
n=57 |
n=73 |
n=333 |
Effective |
68 |
62 |
46 |
48 |
61 |
285 |
| Improved |
5 |
7 |
7 |
4 |
7 |
30 |
No Effect |
73 |
69 |
53 |
52 |
68 |
315 |
| Total Effective Rate |
97.33% |
97.18% |
92.98% |
91.23% |
93.15% |
95.59% * |
Table
5. Comparison of therapeutic effects between
Propranolol Contrast Group
and CardioPhase Group A. (*P>0.05, Ridit analysis). |
As shown in Table 5, CardioPhase
was found to reduce myocardial damage while markedly improving
clinical symptoms. Ridit analysis reveals that improvement
of symptoms was significantly higher in the CardioPhase
Group A as compared to the Propranolol Contrast
Group (P<0.05).
Table 6.
Therapeutic
Effect |
Angina |
Arrhythmia |
Breath
Holding |
Dizziness |
Shortness
of Breath |
Total |
| |
n=233 |
n=241 |
n=212 |
n=203 |
n=250 |
n=1139 |
Effective |
203 |
224 |
193 |
184 |
228 |
1032 |
| Improved |
12 |
12 |
11 |
11 |
17 |
63 |
No Effect |
18 |
5 |
8 |
8 |
5 |
44 |
| Total Effective Rate |
92.27% |
97.93% |
96.23% |
96.06% |
98% |
96.14% |
Table
6. Effects on symptoms in CardioPhase Group
C (All). |
Table 6 shows that CardioPhase
can reduce myocardial damage and markedly improve clinical
symptoms at the same time.
Effects
on Blood Pressure and Heart Rate
Table 7 shows how patients’ blood pressure
was regulated in each group.
Table 7.
| |
Group |
Before
Treatment |
After
Treatment |
t |
P |
| Systolic
Blood
Pressure |
Propranolol Contrast Group |
142.1 ± 21.6 |
127.9 ± 15.2 |
3.72 |
<0.01 |
CardioPhase
Group A |
137.6 ± 21.0 |
130.1 ± 15.8 |
3.52 |
<0.05 |
CardioPhase
Group C |
134.1 ± 21.7 |
127.3 ± 15.8 |
2.78 |
<0.05 |
Diastolic
Blood
Pressure |
Propranolol Contrast Group |
86.6 ± 13.1 |
79.8 ± 8.6 |
3.05 |
<0.01 |
CardioPhase
Group A |
83.3 ± 11.1 |
79.6 ± 9.4 |
2.80 |
<0.05 |
CardioPhase
Group C |
82.8 ± 10.7 |
78.8 ± 12.1 |
2.63 |
<0.05 |
Table
7. Comparison of blood pressure before and
after treatment
among the groups (x ± s). |
Table 8 illustrates how heart
rates in the contrast group were reduced, while the CardioPhase-treated
groups did not show a similar effect. There was extremely
significant difference between the treated-group and the contrast
group (P<0.01).
Table 8.
Group |
Before
Treatment |
After
Treatment |
t |
P |
Propranolol Contrast Group |
84.60 ± 13.71 |
73.79 ± 9.67* |
4.86 |
<0.01 |
CardioPhase
Group A |
81.98 ± 13.41 |
78.63 ± 8.92 |
2.06 |
>0.05 |
CardioPhase
Group C |
83.2 ± 13.52 |
76.47 ± 9.03 |
1.65 |
>0.05 |
Table
8. Comparison of heart rates before and after
treatment among groups. |
Changes
in Laboratory Observations
No change of urine or blood
chemistry was observed in either the CardioPhase or propranolol
treated patients before and after the study, nor were any
changes in chest X-rays observed. The effects of CardioPhase
and propranolol on the plasma LPO and blood erythrocyte SOD
are presented in Tables 9 and 10.
Table 9.
| |
Group |
n |
Before
Treatment |
After
Treatment |
t |
P |
| High
SOD
Patients |
Propranolol Contrast Group |
10 |
1222.70±43.42 |
1129.53±43.70 |
1.40 |
>0.05 |
CardioPhase
Group A |
12 |
1189.00±29.64 |
1107.00±36.60 |
1.10 |
>0.05 |
| Low
SOD
Patients |
Propranolol Contrast Group |
20 |
824.63±26.53 |
869.68±29.35 |
1.60 |
>0.05 |
CardioPhase
Group C |
18 |
862.00±21.53 |
1002.00±42.37* |
2.48 |
<0.05 |
*P<0.01, u = 4.40, in the comparison
before and after treatment.
Table 9. Changes in blood erythrocyte
SOD concentrations before and after treatment between
the Propranolol Group and the CardioPhase Group A
(SOD U/mg Hb, x ±s).
|
Table 9 illustrates changes
in blood erythrocyte SOD concentrations before and after treatment
in CardioPhase Group A and the Propranolol Contrast Group
(SOD U/mg Hb, ±s).
Table 10.
| |
Group |
n |
Before
Treatment |
After
Treatment |
t |
P |
| Elevated
LPO
Patients |
Propranolol Contrast Group |
9 |
2.75 ± 0.19 |
2.60 ± 0.17 |
0.58 |
>0.05 |
CardioPhase
Group A |
10 |
2.72 ± 0.16 |
2.04 ± 0.21* |
2.60 |
<0.05 |
| Low
LPO
Patients |
Propranolol Contrast Group |
21 |
1.34 ± 0.08 |
1.44 ± 0.11 |
0.71 |
>0.05 |
CardioPhase
Group C |
21 |
1.36 ± 0.09 |
1.47 ± 0.11 |
0.71 |
>0.05 |
*P<0.01, u = 10, in the comparison
before and after treatment.
Table 10. Changes in plasma LPO
concentrations before and after treatment between
the Propranolol Group and the CardioPhase Group A
(nmol MAD/ml, x ± s).
|
Tables 9 and 10 show that
CardioPhase increased SOD activity in patients with low SOD
values and decreased LPO concentrations in patients with high
levels of LPO. No such effects were observed in the propranolol-treated
group. Extremely significant differences exist between these
two groups (P<0.01).
Analysis
of Adverse Responses
Of the 304 patients treated with CardioPhase three cases were
observed with dry mouth, two cases with nausea, two cases
with loose stool and two cases with constipation. All issues
were resolved with cessation of use following completion of
the study period. No other adverse responses were observed.
There was no significant difference observed in liver and
kidney functions prior to and following treatment (P>0.05),
illustrating that CardioPhase can be safely applied.
Effects
of CardioPhase on Heart Function
A study comparing the hemodynamic effects of CardioPhase on
32 patients with Congestive Heart Failure (CHF) was performed
using Swan-Ganz catheter. Measurements 1~4 hours after administration
showed reductions in Mean pulmonary arterial pressure (MPAP)
and pulmonary capillary wedge pressure (PCWP), and an increase
in cardiac index (CI). These results were significantly different
from those of the control cases.
A second study comparing cardiac
function, microcirculation and blood viscosity in patients
with myocardial damage was performed using ZXG-40 noninvasive
cardiovascular function diagnostic instrument. The results
showed that CardioPhase strengthened cardiac pump function,
increased blood flow in the coronary artery, elevated myocardial
blood flow, decreased blood viscosity and improved microcirculation.
Discussion
Myocardial damage caused by organic cardiopathy will lead
to cardiac insufficiency or alterations of ECG. Among 304
patients with myocardial damage treated with CardioPhase,
100 cases were observed to have marked improvement, 189 cases
improved and 15 cases were without improvement. The total
effective rate was 95.06%.
Observing electrocardiogram
(ECG) readings after treatment with CardioPhase revealed that
86 patients showed marked improvement, 104 were improved and
114 were without improvement, for a total effective rate of
62.50%.
The therapeutic effect in the
CardioPhase Group A of 100 patients was better than that in
the Propranolol Contrast Group of 100 patients.
Only nine cases among the 304
patients treated by CardioPhase were observed with mild side
effects, which included dry mouth, nausea, loose stool or
constipation. No other adverse responses were observed.
We also observed that CardioPhase
has no adverse effect on liver and kidney function, nor on
routine blood analysis of patients. Our study also showed
that CardioPhase can eliminate clinical symptoms, normalize
blood pressure and improve myocardial microcirculation without
affecting heart rate.
CardioPhase shown to enhance
blood SOD activity and reduce plasma LPO concentrations, indicating
that it is an effective agent for improving and restoring
myocardial functions. The observation of hemodynamic effects
of CardioPhase on some of the patients illustrated that CardioPhase
has a positive inotropic function, reducing pulmonary arterial
pressure and pulmonary capillary wedge pressure. Therefore,
we conclude that CardioPhase can be safely used as an effective
medicine in treating myocardial damage caused by various organic
cardiopathies.
Acknowledgements
This work was supported by Director WANG Hua-liang from the
Cardiovascular Department of the First Affiliated Hospital
of Tianjing Medical Collage, Vice-director SU Ya-qing from
Cardiovascular Department of Affiliated Hospital of Shaanxi
TCM Research Institute, Director YANG Kai-guang from Cardiovascular
Department of Shaanxi Hospital, Director JIA Li-hui from Xi’an
Central Hospital, Vice-director CUI Hua-rong from Cardiovascular
Department of the First Hospital of Xi’an, as well as
Department of Cardiovascular and Geriatrics of the First Affiliated
Hospital of Xi’an Medical Univeristy. The author would
like to thank them for technical assistance. |
